Fluoride-mediated phosphination of alkenes and alkynes by silylphosphines

Article abstract of DOI:10.1016/j.tetlet.2004.10.098

Regioselective phosphination of carbon-carbon unsaturated bonds by a fluoride-mediated reaction of silylphosphines is described. Alkenes and alkynes having a directing group, such as an aromatic or a carbonyl group, reacted to form a carbon-phosphorus bon

Full text of DOI:10.1016/j.tetlet.2004.10.098

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 9167–9169
Fluoride-mediated phosphination of alkenes and
alkynes by silylphosphines
Minoru Hayashi,* Yutaka Matsuura and Yutaka Watanabe*
Department of Applied Chemistry, Faculty of Engineering, Ehime University, 3 Bunkyo-cho, Matsuyama 790-8577, Japan
Received 15 September 2004; revised 18 October 2004; accepted 20 October 2004
Abstract—Regioselective phosphination of carbon–carbon unsaturated bonds by a fluoride-mediated reaction of silylphosphines is
described. Alkenes and alkynes having a directing group, such as an aromatic or a carbonyl group, reacted to form a carbon–phos-
phorus bond under mild conditions. When an anhydrous fluoride source was applied in the presence of an electrophile, the corre-
sponding three-component coupling product was obtained.
Ó 2004 Elsevier Ltd. All rights reserved.
Tertiary phosphines are indispensable as ligands for
transition-metal catalysts; therefore, new methods for
providing multi-functional phosphine ligands, by form-
ing carbon–phosphorus bonds under mild conditions
have received great attention.1 In general, conventional
synthetic methods, including Grignard reagents or alka-
line metal phosphides, have been limited to simple alkyl
and aryl phosphines due to spontaneous reactivities of
these reagents.2
ide-mediated reaction of silylphosphines as a novel
phosphination of carbon–carbon unsaturated bonds.
We first surveyed the reactivity of silylphosphine 28
toward styrene in the presence of TBAF (commercial 1.0
M solution in THF) under several conditions (Table 1).
TBAF
Ph
+
Ph
Ph P SiMe tBu
2
2
PPh
2
2
The diphenylphosphino group of 2 selectively added to
the b-position of styrene resulting in diphenyl(2-phenyl-
ethyl)phosphine. The most influential factor in the reac-
tion was the solvent used. In CH2Cl2, only 8% of the
product was formed even after 4h under reflux. In con-
trast, the addition proceeded smoothly and rapidly at
room temperature in polar solvents, such as DMF and
DMSO. Although the use of CH3CN gave a poor result
at rt, the reaction proceeded well at 50°C. In all the
cases, no reaction occurred in the absence of TBAF.
Silylphosphines offer considerable potential as synthetic
equivalents of phosphines, masked phosphines, or phos-
phides, for the synthesis of several organophosphorus
compounds.3 The silylphosphines themselves generally
have a much lower reactivity, in comparison with other
metal phosphides, such as lithium phosphides. However,
some silylphosphines easily react with good electro-
philes, such as an aldehyde,4 an acyl halide,5 a,b-unsatu-
rated carbonyl compounds,6,7 and an azodicarboxylate.8
The nucleophilicity of a phosphorus atom of a silylphos-
phine should increase upon treatment with a fluoride
anion and the resulting agent could serve as a powerful
phosphorus nucleophile. Despite the great utility of fluor-
ide anion for activation of organosilicon compounds,
a fluoride-mediated reaction of silylphosphines has not
been reported thus far. In this study, we report a fluor-
The results of the fluoride-mediated phosphination of
several alkenes, including the conjugated ones, are
shown in Table 2.9
Table 1. Solvent effects on the phosphination reaction
Entry
Solvent
Temp. (°C)
Time (min)
Yield (%)
1
2
3
4
5
CH2Cl2
CH3CN
CH3CN
DMF
40
25
50
25
25
240
120
20
8
36
81
89
81
Keywords: Silylphosphine; Phosphination; Michael addition; Three-
component coupling.
15
20
*
Corresponding authors. Tel.: +81 89 927 9917; fax: +81 89 927
9944; e-mail: hayashi@eng.ehime-u.ac.jp
DMSO
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.10.098

9168
M. Hayashi et al. / Tetrahedron Letters 45 (2004) 9167–9169
Table 2. Fluoride-mediated phosphinationa
Entry
1
Substrate
Product
Yield (%)b
89
1a
1b
Ph
Ph
3a
3b
Ph P
2
2
95
Ph P
2
N
N
3
4
Ph
1c
1d
3c
3d
78
82
Ph
Ph P
2
CO Et
2
CO Et
2
Ph P
2
Ph
76c
CO Me
2
5
1e
3e
CO Me
2
Ph
Ph P
2
CN
CN
6
7
1f
3f
81
76
Ph P
2
CONMe
O
2
CONMe
O
1g
3g
2
Ph P
2
Ph P
2
8
9
1h
1i
3h
3i
78c
O
Ph P
O
2
75c,d,e
75d,f
62d,g
Ph
Ph
10
11
4a
4b
5a
5b
H
Ph
Ph P
2
n-Bu
n-Bu
Ph
Ph P
2
a All reactions were conducted in DMF at rt for 15min, using 1.2equiv of silylphosphine and TBAF each. A commercial 1.0M THF solution of
TBAF (contains ca. 5% of water) was used.
b Isolated yields.
c Phosphine adducts formed initially were easily oxidized after purification.
d The ratio of the isomers was determined by 31P NMR.
e The ratio of isomers was trans/cis >95:5.
f The ratio of the E and Z isomers was ca. 5:1.
g The ratio of the E and Z isomers was ca. 3:2.
This reaction required an aromatic group or an electron-
withdrawing group on the alkene; an alkene having only
an alkyl group did not react with 2 at all. This was prob-
ably due to lack of stabilization of an anionic intermedi-
ate during addition. Aromatic alkenes, a, b-unsaturated
carbonyls, and a nitrile reacted in 15min resulting in
good yields of the corresponding b-phosphino adducts
(entries 1–9).10 Substituents on the b-carbon did not
affect the addition (entries 3, 5, 8, and 9). Methyl cinna-
mate gave methyl 3-phenyl-3-(diphenylphosphino)pro-
pionate, which indicated that the carbonyl group is a
better directing group than the phenyl group of the cin-
namate (entry 5).
trimethylsilyldiphenylphosphine 6 instead of 2 provided
almost the same results; for example, addition of 6 to
ethyl acrylate 1d and ethynylbenzene 4a under the same
conditions gave 3d (78%) and 5a (64%), respectively.
The reaction appeared to proceed through tetra-n-butyl-
ammonium diphenylphosphide generated in situ from
silylphosphine and TBAF. The characteristic red color
of the diphenylphosphide appeared on addition of
TBAF to the solution of silylphosphine and this soon
faded as the reaction progressed. Since the commercial
TBAF solution contains a small amount of water, the
substituent-stabilized intermediate, which is formed by
subsequent addition to an alkene, may be trapped by
protonation. When an additional electrophile exists in
the absence of a proton source, the intermediate should
be trapped by the electrophile. In fact, the three-compo-
nent coupling reaction of benzaldehyde, 2, and 1d was
accomplished using TASF as an anhydrous fluoride
resulting in good yields of 7 (Scheme 1) as a mixture
of diastereomers.11
This fluoride-mediated phosphination could be success-
fully applied to alkynes. Alkynes 4a and 4b resulted in
the corresponding adducts 5a and 5b in a regioselective
manner, as a mixture of E/Z isomers (entries 10 and 11).
At least one directing group was also required in the
case of alkynes; a terminal aliphatic alkyne did not react
at all.
In addition, the reactivity did not depend on the substit-
uents on the silyl group of the silylphosphine. Use of
The addition did not proceed without a second electro-
phile, such as an aldehyde or a proton source. These

M. Hayashi et al. / Tetrahedron Letters 45 (2004) 9167–9169
9169
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CO2Et
1d
+
Ph2P
TASF
DMF
t
Ph2PSiMe2 Bu
2
CO2Et
Ph2P
OH
Ph
CO2Et
7 97%
PhCHO
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(d.r. = 3 : 2)
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results clearly suggested that equilibrium may exist at
the first addition step. Then, the stabilized intermediate
successively added to the electrophile resulting in
the adduct.
9. Typical procedure: Silylphosphine 2 (72mg, 0.24mmol) in
DMF (1.5mL) and THF solution of tetra-n-butylammo-
nium fluoride (1.0M, 0.2mL) were added to a stirred
mixture of styrene 1a (21mg, 0.2mmol) at rt. After stirring
for 15min at rt, the solvent was removed in vacuo. The
residue was purified by column chromatography on silica
gel (eluent: CHCl3/n-hexane = 1:4, Rf 0.4) resulting in
adduct 3a (47mg, 89%), which is a colorless oil.
The phosphination of carbon–carbon unsaturated
bonds is of interest in recent times, due to the wide
use of functional phosphines as ligands in catalysis.12,13
Base-catalyzed,14 metal-catalyzed,15 and uncatalyzed16
phosphination of alkenes and alkynes have been exten-
sively studied in recent years. The present fluoride-medi-
ated phosphination proceeded smoothly under quite
mild conditions. It produced results similar to other
methods for simple addition, in terms of yields and
selectivities. Moreover, it has the advantage that the car-
bon frame of the adduct can be extended through the
subsequent coupling reaction in one pot, thereby result-
ing in more functionalized phosphines.
10. Blinn, D. A.; Button, R. S.; Ferazi, V.; Neeb, M. K.;
Tapley, C. L.; Trehearne, T. E.; West, S. D.; Kruger, T. L.;
Storhoff, B. N. J. Organomet. Chem. 1990, 393, 143–152.
11. Typical procedure: TASF (134mg, 0.50mmol) was added
to a stirred mixture of 1d (42mg, 0.42mmol), silylphos-
phine 2 (150mg, 0.50mmol), and benzaldehyde (43mg,
0.42mmol) in DMF (3mL) at rt. After stirring for 3h at rt,
the solvent was removed in vacuo. The residue was
purified by column chromatography on silica gel (eluent:
AcOEt/n-hexane = 1:4) resulting in adduct 7 (160mg,
97%) as a mixture of diastereomers (isomer ratio = 3:2),
In conclusion, we have developed a novel phosphination
reaction of alkenes and alkynes by silylphosphines that
is mediated by TBAF. Formation of a carbon–phospho-
rus bond through a mild and convenient procedure has
paved the way for obtaining a variety of new multi-func-
tional organophosphorus compounds, particularly lig-
ands of transition metal catalysts.
1
which is difficult to separate; (major isomer) H NMR d
1.14 (t, J = 7.7Hz, 3 H), 2.81 (t, J = 5.1Hz, 2H), 3.10 (dt,
J = 7.6, 5.1Hz, 1H), 3.92 (m, 2H), 4.90 (d, J = 7.6Hz, 1H),
7.27–7.51 (m, 10H), 7.60–7.73 (m, 5H); 13C NMR d 13.6,
29.1 (d, J = 70.8Hz), 47.9 (d, J = 2.5Hz), 60.9, 75.2 (d,
J = 8.5Hz), 126.5, 127.9, 128.6 (d, J = 4.1Hz), 128.8, 130.7
(d, J = 9.6Hz), 131.2 (d, J = 9.7Hz), 132.1 (d, J = 2.4Hz),
132.7, 141.2, 172.8 (d, J = 6.7Hz); 31P NMR d À18.4; IR
(neat) 3091, 3048, 3004, 2956, 1730, 1591, 1448, 1320,
1251, 1032, 781, 704cmÀ1; FABMS calcd for C24H25O3P,
Acknowledgements
The authors thank Venture Business Laboratory of
Ehime University for their financial support. We also
thank Center for Cooperative Research and Develop-
ment, Ehime University for measurement of mass spec-
tra. This work was supported by the Fujisawa
Foundation and Saneyoshi Scholarship Foundation.
1
392; found 393 (M + H). (minor isomer) H NMR d 1.05
(t, J = 8.0Hz, 3 H), 2.35 (m, 2H), 3.80 (m, 2H), 5.14 (d,
J = 4.8Hz, 1H), 7.23–7.51 (m, 10H), 7.60–7.73 (m, 5H);
31P NMR d À19.2. These two diastereomers could be
separated by a column chromatography on silica gel
(eluent: AcOEt/n-hexane = 3:2) as their phosphine oxides
after oxidation by mCPBA.
12. Alonso, F.; Beletsukaya, I. P.; Yus, M. Chem. Rev. 2004,
104, 3148–3150.
13. Wicht, D. K.; Glueck, D. S. In Catalytic Heterofunction-
Supplementary data
alization; Togni, A., Grutzmacher, H., Eds.; Wiley-VCH
¨
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.2004.
10.098.
Verlag GmbH: Weinheim, 2001; pp 143–170.
14. Bunlaksananusorn, T.; Knochel, P. Tetrahedron Lett.
2002, 43, 5817–5819.
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G.; Komeyama, K.; Takeda, M.; Shishido, T.; Kitani, A.;
Takehira, K. J. Org. Chem. 2003, 68, 6554–6565.
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