A novel stereoselective synthesis of (E)-2-arylvinylphosphonates in InCl3-NaBH4-MeCN system

Article abstract of DOI:10.1016/j.jorganchem.2005.01.024

Hydroindation of arylalkynylphosphonates gives a intermediate which can be hydrolyzed to (E)-2-arylvinylphosphonates in InCl₃-NaBH ₄-MeCN system, the stereoselectivity and yield are rather high, but under the same conditions 2-alkylalkynylphosphonates do not react very well.

Full text of DOI:10.1016/j.jorganchem.2005.01.024

Journal of Organometallic Chemistry 690 (2005) 1705–1709
www.elsevier.com/locate/jorganchem
A novel stereoselective synthesis of (E)-2-arylvinylphosphonates in
InCl3–NaBH4–MeCN system
*
Chunyan Wang, Yuanjiang Pan , Deyu Yang
Department of Chemistry, Zhejiang University (Yuquan campus), Hangzhou 310027, PR China
Received 15 December 2004; accepted 18 January 2005
Available online 8 March 2005
Abstract
Hydroindation of arylalkynylphosphonates gives a intermediate which can be hydrolyzed to (E)-2-arylvinylphosphonates in
InCl3–NaBH4–MeCN system, the stereoselectivity and yield are rather high, but under the same conditions 2-alkylalkynylphos-
phonates do not react very well.
ꢀ 2005 Elsevier B.V. All rights reserved.
Keywords: InCl3–NaBH4–MeCN system; Hydroindation; (E)-2-Arylvinylphosphonates; Stereoselectivity; Alkynylphosphonates
1. Introduction
phosphonates could also be prepared by olefin cross-
metathesis. (Z)-Vinylphosphonates could be prepared
by addition of ‘‘zirconocene’’ to alkynylphosphonates
and hydrolysis [9]. Recently it has been reported that
Palladium-catalytic coupling reactions of bro-
moalkenylphosphonates with aryl boronic acids and
alkenyl borates or using vinylboronates both gave vinyl-
phosphonates [10]. Even now, a new and high stereose-
lective synthetic method for vinylphosphonates would
be valuable. In this paper, we would present a synthetic
method of (E)-2-arylvinylphosphonates.
Since dichloroindium hydride (Cl2InH) was pre-
pared firstly and applied in organic synthesis, it has re-
ceived more and more attention [11]. Recently,
dichloroindium hydride (Cl2InH) generated in situ
from the combination of sodium borohydride and a
catalytic amount of indium trichloride has been dem-
onstrated to be a benign alternative to InCl3/n-Bu3SnH
system [12]. InCl3–NaBH4–MeCN system is easy to
handle and has low toxicity compared to the latter.
So it has been applied in organic synthesis widely, such
as the dehalogenation of alkyl halides and other radical
cyclizations [13], the cross-coupling reaction of termi-
nal alkynes with iodides [14], dimerization of terminal
Vinylphosphonates have been widely used as syn-
thetic intermediates in organic chemistry [1] and investi-
gated as biologically active compounds [2], especially in
stereoselective synthesis of trisubstituted olefins [3] and
heterocycle compounds [4]. Up to now, the synthesis
of vinylphosphonates has been explored extensively.
However the synthesis methods include a variety of
non-catalytic reactions [5] and palladium-catalytic
cross-coupling reactions [6], these methods are limited
by the requirement of highly active functional groups
in the substrates. For example, 2-arylvinylphosphonates
can be also prepared by the palladium-catalyzed aryla-
tion of diethyl vinylphosphonate with aryl bromides
[7], but this synthetic route gives a mixture of (E)-vinyl-
phosphonates and (Z)-vinylphosphonates. Palladium-
catalyzed phosphonylation of (E)-a-haloolefins could
give (E)-2-arylvinylphosphonates, in which the starting
material is not easily available [8]. In addition, vinyl-
*
Corresponding author. Tel./fax: +86 571 87951264.
E-mail address: cheyjpan@zju.edu.cn (Y. Pan).
0022-328X/$ - see front matter ꢀ 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2005.01.024

1706
C. Wang et al. / Journal of Organometallic Chemistry 690 (2005) 1705–1709
alkynes [15]. Now, this paper wants to present a stere-
oselective synthesis of (E)-2-arylvinylphosphonates by
hydroindation of 2-arylalkynylphosphonates in InCl3–
NaBH4–MeCN system.
formed at À15 ꢁC to r.t. Excess of NaBH4 gave higher
stereoselectivity and conversion. To our surprise, when
1 mmol iodobenzene was added, the main product was
(Z)-phenylvinylphosphonates (IIa). Because of the pro-
pensity of the lower valent group 13 metals to form com-
plexes with aryl rings benzene and toluene were added to
the reaction mixture respectively. But the stereoselectiv-
ity and conversion have no change compared to entry 9.
When 1 mmol iodine was added, no expectant com-
pound was obtained. The rational explanation is not
clear so far. The results were listed in Table 1.
Under the same conditions [InCl3 (1 mmol), NaBH4
(2 mmol), MeCN (10 ml), À15 ꢁC to r.t., 15 h], we exam-
ined a variety of alkynylphosphonates (Scheme 2). It
was found that when R was Ph or cyclohexenyl, the
yield and the stereoselectivity were both satisfactory.
When the hydrogen atom of benzene ring was substi-
tuted by methyl group (d, f), the stereoselectivity
decreased slightly, while hydrogen atom of benzene ring
was substituted at the para position by fluorine atom (g)
the yield and the selectivity were rather high. When R
was aliphatic such as n-C4H9 or c-C3H5 the yield
decreased greatly. Even if the equivalent ratio of InCl3
and alkynylphosphonates was increased to 1.5:1, the
yield and stereoselectivity of reactions b or c were not
improved (Table 2). The spectra data of the known
products were consistent with the references cited [16].
2. Results and discussion
Initially, we optimized the reaction conditions involv-
ing the reaction temperature and equivalence of NaBH4.
Phenylalkynylphosphonate was employed as model in
these reactions (Scheme 1). The reactions were moni-
tored by TLC. The products were purified by silica gel
column chromatography. The conversion and the ratio
of (E)-phenylvinylphosphonates (Ia) and (Z)-phen-
ylvinylphosphonates (IIa) were detected by 1H NMR
and HPLC-MS. The stereostructure was determined
by the coupling constant between two trans vinyl pro-
tons (J = 17.59 Hz) of (E)-phenylvinylphosphonates
(Ia), which was consistent with the literature reported
in the references cited [6]. As shown in Table 1, the en-
tries 1 and 2 suggested that InCl3 could play a catalytic
role in this reaction. However, the yields were very low.
So the equivalent mole of InCl3 with the substrate was
selected. Entries 3, 6 and 9 optimized the mole ratio of
NaBH4 with the substrate. At the same time the best
conversion was observed when the reaction was per-
H
PO(OEt)
H
Ph
2
Ph
InCl -NaBH -MeCN brine
3
4
+
Ph
PO(OEt)
2
T
H
PO(OEt)
H
2
I
II
a
a
Scheme 1.
Table 1
Studying of the system in reduction of 2-phenylalkynylphosphonates
Yield (%)b
a,b
Entry
T
InCl3:NaBH4:alkyne
Ia/IIa
1
2
À15 to r.t.
À15 to r.t.
À15 to r.t.
r. t.
1:10:10
1:10:5
1:10:1
1:10:1
1:10:1
1:5:1
100/0
100/0
>98/2
–
53
52
99
–
3
4
5
0 to r.t.
>98/2
98/2
98/2
94
93
93
95
95
88
–
6
À15 to r.t.
0 to r.t
0 to r.t
7
8c
1:5:1
1:5:1
42/58
100/0
89/11
–
9
À15 to r.t.
0 to r.t
1:2:1
1:2:1
10
11d
12e
13f
a
À15 to r.t.
À15 to r.t.
À15 to r.t.
1:2:1
1:2:1
>99/1
>99/1
96
96
1:2:1
Determined by 1H NMR (500 MHz).
Determined by HPLC-MS.
b
c
d
e
f
1 mmol iodobenzene was added.
1 mmol iodine was added.
1 mmol benzene was added.
1 mmol toluene was added.

C. Wang et al. / Journal of Organometallic Chemistry 690 (2005) 1705–1709
1707
R
H
PO(OEt)2
H
R
InCl3-NaBH4-MeCN brine
+
PO(OEt)2
R
-15 ˚C - r. t.
15 hrs
H
H
PO(OEt)2
II
I
R: Ph, n-C4H9, c-C3H5, p-CH3C6H5,
Scheme 2.
, o-CH3C6H5
Table 2
Synthesis of vinylphosphonates in InCl3–NaBH4–MeCN system
Entry
R
I/IIa,c
Total yield (%)a,c
a
Ph
100/0
15/1
11/2
7/1
95
10
b
n-C4H9
c-C3H5
n-C4H9
c-C3H5
p-CH3C6H5
c
38
22
bb
cb
d
14/1
89/11
99/1
92/8
100/0
46
99
e
97
96
f
o-CH3C6H5
p-FC6H5
g
100
Reaction conditions: InCl3 (1 mmol), NaBH4 (2 mmol), MeCN (10 ml), arylalkynylphosphonates (1 mmol), À15 ꢁC to r.t., 15 h, brine (5 ml).
a
Determined by 1H NMR (500 MHz).
b
InCl3 (1.5 mmol), NaBH4 (3 mmol), MeCN (10 ml), arylalkynylphosphonates (1 mmol).
Determined by HPLC-MS and GC-MS.
c
When quenched with D2O the reaction mixture
obtained from Phenylalkynylphosphonate with InCl3–
NaBH4 system (the same condition with a) yielded
(E)-phenylvinylphosphonates in 57% yield, 1-D-
(E)-phenylvinylphosphonates in 42%, together with
trace (Z)-phenylvinylphosphonates and 1-D-(Z)-
phenylvinylphosphonates (the total yield was less than
1%) (Scheme 3). According to all this results, the radical
mechanism of hydroindation process was proposed
(Scheme 4). The intermediate A is more stable than B.
The radical intermediate in which aryl ring bears the
electron-withdrawing group is more stable than the
intermediate bearing the electron-releasing group.
system was firstly employed in reduction of
alkynylphosphonates successfully. The efficiency and
operational simplicity of the presented method make it
useful and attractive for the synthesis of (E)-2-
arylvinylphosphonates.
3. Experimental
1H NMR spectra were obtained with a Bruker
AVANCE DMX-500 NMR spectrometer in CDCl3 as
a solvent, with TMS as an internal standard. The ESI-
plus
MS spectra were taken on a Bruker Esquire 3000
In summary, a new and simple approach to (E)-2-aryl-
vinylphosphonates from (E)-2-arylalkynylphosphonates
has been developed, in which the InCl3–NaBH4–MeCN
spectrometer. HPLC was performed on Aligent 1100.
Precoated thin-layer plates of silica gel 60 GF254 (Qing-
dao Haiyang Chemical Co. Ltd., Qingdao, China.) were
H
Ph
D
Ph
InCl3-NaBH4-MeCN D2O
+
Ph
PO(OEt)2
H
PO(OEt)2
-15˚C - r. t. 15 hrs
H
PO(OEt)2
42%
Yield: 57%
PO(OEt)2
H
PO(OEt)2
Ph
Ph
+
+
H
H
D
<1%
Scheme 3.

1708
C. Wang et al. / Journal of Organometallic Chemistry 690 (2005) 1705–1709
R
CPO(OEt)2
InCl2
R
H
RC
PO(OEt)2
.
.
InCl2
+
.
H
PO(OEt)2
H
C
B
A
R
InCl2
R
.
.
+
InCl2
PO(OEt)2
H
H
PO(OEt)2
D
C
A
R
H
PO(OEt)2
R
H
PO(OEt)2
InCl2
.
.
InCl2
+
E
C
B
R
InCl2
PO(OEt)2
H(D)
R
H
R
H2O(D2O)
PO(OEt)2
InCl2
PO(OEt)2
H(D)
R
+
PO(OEt)2
H
H
H
E
D
Scheme 4.
used for analytical purposed. GC-MS data were re-
corded by TRACE 2000 GC/ MS(USA TRACE com-
pany). Acetonitrile was freshly distilled from
phosphorus pentoxide before use. Alkynylphosphonates
were prepared according to the literature [17].
References
[1] T. Minami, J. Motoyoshiya, Synthesis (1992) 333.
[2] B. Stowasser, K.–H. Budt, J.-Q. Li, A. Peyman, D. Ruppert,
Tetrahedron Lett. 33 (1992) 6625;
R. Hirschmann, A.B. Smith, C.M. Taylor, P.A. Benkovic, S.D.
Taylor, K.M. Yager, P.A. Sprengeler, S.J. Benkovic, Science 265
(1994) 234;
InCl3 (1 mmol), dry MeCN (10 ml) and NaBH4 (2
mmol) were mixed at À15 ꢁC under nitrogen. After
the mixture was stirred for 30 min, alkynylphosphonates
(1 mmol) was added by syringe. The cooling bath was
removed. The reaction mixture was warmed to the room
temperature, stirred for 15 h. The reaction was moni-
tored by TLC. In order to destroy the excessive NaBH4
brine (5 ml) was added to the reaction mixture. The
reaction mixture was stirred for 10 min, filtered. The fil-
trate was extracted by ether (20 ml · 3). The combined
organic layer was dried over MgSO4 and concentrated
in vacuum. Purification by silica gel column (100–200
mesh), using petroleum ether / ethyl acetate (3:1) as elu-
ent could afford the corresponding products.
1H NMR (500 MHz, CDCl3) data for Ic: dH = 0.93
(m, 4H), 1.35 (t, 6H, J = 7.0 Hz), 1.58 (m, 1H), 4.13
(quin, 4H, J = 7.0 Hz), 6.21 (m, 1H); MS (ESI): 204.7
[M + H]+, 226.7 [M + Na]+, 242.8 [M + K]+.
1H NMR (500 MHz, CDCl3) data for Ie: dH = 1.37 (t,
6H, J = 7.0 Hz), 1.65 (m, 6H), 2.16 (m, 4H), 4.16 (m,
4H), 5.52 (t, 1H, J = 18.0 Hz), 6.12 (s, 1H), 7.09 (m,
1H); MS (ESI): 244.9 [M + H]+, 266.9 [M + Na]+,
282.9 [M + K]+.
R.T. Wester, R.J. Chambers, M.D. Green, W.R. Murphy, Bioorg.
Med. Chem. Lett. 4 (1994) 2005.
[3] Y. Shen, G.–F. Jiang, Synthesis (2000) 99;
K. Tago, H. Kogen, Org. Lett. 2 (2000) 1975.
[4] R. Kouno, T. Okauchi, M. Nakamura, J. Ichikawa, T. Minami,
J. Org. Chem. 63 (1998) 6239;
R. Kouno, T. Tsubota, T. Okauchi, T. Minami, J. Org. Chem. 65
(2000) 4326.
[5] M.F. Probst, A.M. Modro, T.A. Modro, Can. J. Chem. 75 (1997)
1131;
J.M. Gil, D.Y. Oh, J. Org. Chem. 64 (1999) 2950;
P. Zhong, X. Huang, Z.X. Xiong, Synlett (1999) 721;
A. Otaka, E. Mitsuyanma, H. Watanabe, H. Tamamura, N.
Fujii, Chem. Commun. (2000) 1081;
L.A. Braga, E.F. Alves, C.C. Silverira, L.L. de Andrade,
Tetrahedron Lett. 41 (2000) 161;
W.B. Jang, D.Y. Oh, C.–W. Lee, Tetrahedron Lett. 41 (2000)
5103.
[6] D.A. Holt, J.M. Erb, Tetrahedron Lett. 30 (1989) 5393;
L.–B. Han, M. Tanaka, J. Am. Chem. Soc. 118 (1996) 1571;
M.A. Kazankova, I.G. Trostyanskaya, S.V. Lutsenko, I.P.
Beletskaya, Tetrahedron Lett. 40 (1999) 569;
T. Okauchi, T. Yano, T. Fukamachi, J. Ichikawa, T. Minami,
Tetrahedron Lett. 40 (1999) 5337;
P. Zhong, Z.X. Xiong, X. Huang, Synth. Commun. 30 (2000)
273;
L.–B. Han, F. Mirzaei, C.–Q. Zhao, M. Tanaka, J. Am. Chem.
Soc. 122 (2000) 5407;
H. Brunner, N.L. de Courey, J.–P. Genet, Synlett (2000) 201.
[7] Y. Xu, M.T. Flavin, Z.Q. Xu, J. Org. Chem. 61 (1996) 7697.
[8] T. Hirao, T. Masunaga, T. Ohshiro, T. Agawa, Tetrahedron Lett.
21 (1980) 3595;
Acknowledgement
The generous financial support of Natural Science
Foundation of China (20375036) is gratefully
acknowledged.
T. Hirao, T. Masanaga, N. Yamada, Y. Ohshiro, T. Agawa, Bull.
Chem. Soc. Jpn. 55 (1982) 909.

C. Wang et al. / Journal of Organometallic Chemistry 690 (2005) 1705–1709
1709
[9] A.A.A. Quntar, M. Srebnik, Org. Lett. 3 (2001) 1379.
[10] G.W. Kabalka, S.K. Guchhait, Org. Lett. 5 (2003) 729;
Y. Kobayashi, A.D. William, Org. Lett. 4 (2002) 4241.
[11] T. Miyai, K. Inoue, M. Yasuda, I. Shiubata, A. Baba, Tetrahe-
dron Lett. 39 (1997) 1929.
[14] K. Takami, S. Mikami, H. Yorimitsu, H. Shinokubo, K. Oshima,
J. Org. Chem. 68 (2003) 6627;
K. Takami, H. Orimitsu, K. Oshima, Org. Lett. 4 (2002) 2993.
[15] C.Y. Wang, H. Su, D.Y. Yang, Synlett 3 (2004) 561.
[16] T. Koizumi, N. Tanaka, M. Iwata, E. Yoshii, Synthesis (1982)
917;
[12] K. Inoue, A. Sawada, I. Shibata, A. Baba, J. Am. Chem. Soc. 124
(2002) 906.
Y.Y. Xu, X.L. Jin, G.H. Huang, Y.Z. Huang, Synthesis (1983)
556;
[13] K. Inoue, A. Sawada, I. Shibata, A. Baba, Tetrahedron Lett. 42
(2001) 4661;
B.C. Ranu, S. Samanta, Tetrahedron 59 (2003) 7901.
R. Classen, G. Ha¨gele, J. Fluorine Chem. 77 (1996) 71.
[17] M.S. Chattha, A.M. Aguiar, J. Org. Chem. 36 (1971) 2719.