Fluoride-catalyzed three-component coupling reaction of a silylphosphine, activated alkenes and aldehydes

Article abstract of DOI:10.1016/j.tetlet.2005.05.128

A novel CsF-catalyzed three-component coupling reaction of a silylphosphine, activated alkenes and aldehydes is described. Multi-functional phosphines were obtained by forming both carbon-phosphorus and carbon-carbon bonds in good yields under mild conditions.

Full text of DOI:10.1016/j.tetlet.2005.05.128

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 5135–5138
Fluoride-catalyzed three-component coupling reaction of a
silylphosphine, activated alkenes and aldehydes
Minoru Hayashi,* Yutaka Matsuura and Yutaka Watanabe*
Department of Applied Chemistry, Faculty of Engineering, Ehime University, 3 Bunkyo-cho, Matsuyama 790-8577, Japan
Received 11 May 2005; revised 28 May 2005; accepted 30 May 2005
Available online 16 June 2005
Abstract—A novel CsF-catalyzed three-component coupling reaction of a silylphosphine, activated alkenes and aldehydes is
described. Multi-functional phosphines were obtained by forming both carbon–phosphorus and carbon–carbon bonds in good
yields under mild conditions.
Ó 2005 Elsevier Ltd. All rights reserved.
Table 1. Fluoride-promoted three-component coupling reactiona
A mild and convenient procedure for obtaining a variety
of new multi-functional organophosphorus compounds
have received great attention due to the wide use of these
OR
F-
CO2Et
t
+
+
Ph2PSiMe2 Bu
PhCHO
functional phosphines as ligands in catalysis.1 Forma-
tion of a carbon–phosphorus bond through the phosphi-
nation of carbon–carbon unsaturated bonds is of
interest in recent times.2,3 In addition, a three-compo-
nent coupling reaction including both carbon–phospho-
rus and carbon–carbon bond formation is a quite
promising method to produce a variety of multi-func-
tional phosphines. We have recently reported a novel
phosphination of alkenes and alkynes by use of a fluo-
Ph2P
Ph
DMF
CO2Et
1a
3a
2
4aa : R = H
t
5aa : R = SiMe2 Bu
Entry
Fluoride
TASF
Equiv
Time (h)
4aab
5aab
c
1
2
3
4
5
6
1.2
0.1
1.2
1.2
0.1
0.05
3
4
1
2
3
4
95
—
—
c
c
—
c
c
KF
CsF
—
—
55
9
5
68
67
ride-activated silylphosphine, and
a stoichiometric
three-component coupling reaction with an aldehyde
giving multi-functional phosphines.4 In this study, we
report a novel catalytic version of the three-component
coupling reaction.
8
a The reactions were conducted at rt.
b Isolated yields.
c Not observed.
We first surveyed the reactivity of several kinds of fluo-
ride source toward silylphosphine in the presence of
ethyl acrylate and benzaldehyde as an alkene and an
additional electrophile, respectively (Table 1). As al-
ready reported, stoichiometric reaction using TASF in
DMF proceeded well (entry 1).4 The CsF-mediated reac-
tion in DMF also proceeded smoothly, whereas KF did
not work probably because of its low solubility. Other
solvents, such as CH2Cl2, CH3CN and THF, gave poor
results due to low reactivity of the intermediate phos-
phide in these solvents, as seen in the previous Michael
addition.4
When the reaction was performed with CsF, a small
amount of the silyl ether 5aa was isolated (entry 4). This
result clearly showed that a part of the initially formed
alkoxide of the adduct 4aa attacked the silylphosphine
and reproduced the nucleophilic phosphide.5 Therefore,
we next examined the catalytic reactivity of those fluo-
rides, and found that only CsF promoted the reaction
in a catalytic way to afford the silyl ether 5aa as a main
product together with the parent alcohol 4aa in totally
good yield (entries 5 and 6).
Keywords: Silylphosphine; Phosphination; Michael addition; Three-
component coupling.
*
Corresponding authors. Tel.: +81 89 927 9917; fax: +81 89 927
9944; e-mail: hayashi@eng.ehime-u.ac.jp
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.05.128

5136
M. Hayashi et al. / Tetrahedron Letters 46 (2005) 5135–5138
phosphines easily reacted with aldehydes.6 When the
Ph PSi
2
reaction was attempted in the absence of aldehyde,
CsF did not catalyze the addition; only a trace of the
corresponding adduct 6a was formed instead. Notewor-
thy was that the enolate formed after Michael addition
did not give the silyl enolate, whereas the alkoxide of
the aldol-type adduct smoothly attacked the silylphos-
phine to promote the catalytic cycle (Scheme 1). It is
in contrast to the formation of the silyl enolate in the
reaction of trimethylsilyldiphenylphosphine and acro-
lein.7 An alkoxide, such as sodium methoxide, reacted
with the silylphosphine to produce the corresponding
phosphide, and it indeed catalyzed the three-component
coupling reaction. However, the results of alkoxide-
catalyzed reactions were not satisfactory compared with
the present CsF-catalyzed reaction.
OSi
Ph
CO Et
F
7a
Ph P
2
PhCHO
Ph P
2
2
CO Et
2
Ph PSi
2
Ph PSi
2
O
O
Ph P
2
Ph
CO Et
2
Ph P
2
OEt
PhCHO
Scheme 1.
The results of the CsF-catalyzed coupling of several alk-
enes and carbonyl compounds are shown in Table 2.8,9
The present catalytic reaction proceeded selectively in
one pot because of low reactivity of 2 toward aldehydes
and sufficient nucleophilicity of the phosphide derived
from 2 toward Michael acceptors, although some silyl-
Since the reaction started with Michael-type phosphin-
ation, the alkenes having electron-withdrawing group,
such as typical Michael acceptors like a,b-unsaturated
carbonyl compounds, reacted smoothly to give the corre-
Table 2. CsF-catalyzed three-component coupling reactiona
Entry
Acceptor
Electrophile
Products
Yieldsb (%)
88
drc
OH
Ph
CO2Et
Ph OH
Ph
1
CO2Et
1a
PhCHO
3a
4aa
1:1.5
Ph2P
e
—
72d
85
CO2Et
2
3
4
5
1b
1c
1d
1e
PhCHO
PhCHO
PhCHO
PhCHO
3a
3a
3a
3a
4ba
4ca
4da
4ea
Ph2P
Ph2P
Ph2P
Ph2P
Ph
CO2Et
OH
CONMe2
1:1.2
1:1.3
1:1.3
Ph
CONMe2
OH
80
CN
Ph
CN
OH
CO2nBu
72
Ph
CO2nBu
f
f
6
7
1f
PhCHO
3a
3b
—
—
—
Ph
OH
76g
1:1.2
Ph2P
Ph2P
iPr
CO2Et
CO2Et
1a
iPrCHO
4ab
4ac
OH
Cl
Cl
CHO
Cl
Cl
8
CO2Et
1a
3c
67
1:2
CO2Et
a Unless otherwise noted, the reaction was conducted in DMF at rt for 4 h by using 5 mol% of CsF, an alkene (1.1 equiv) and 2 (1.1 equiv).
b Yields of the alcohol products isolated after hydrolysis of the initially formed silyl ethers.
c Diastereomer ratios were determined by 1H and 31P NMR.
d The adduct was isolated as its oxide because the initially formed adduct 4ba readily oxidized in air. The ratio of diastereomers was determined by
31P NMR.
e Not determined.
f No adduct was formed after 4 h. Extended reaction time resulted in the formation of aldehyde adduct 7a.
g The reaction was continued for 6 h.

M. Hayashi et al. / Tetrahedron Letters 46 (2005) 5135–5138
5137
sponding adducts in fairly good yields (entries 1–5). In
contrast, the alkenes having a weak activating group like
styrene did not give any adduct (entry 6), although sty-
rene smoothly reacted with stoichiometric TBAF in the
presence of proton source to form the corresponding
adduct in good yield.4 Extended reaction time in the
reaction of styrene resulted in the formation of 7a via di-
rect addition to the aldehyde. Michael acceptors having
an acidic proton, such as cyclohexenone, gave no three-
component coupling adducts. In these cases, simple
Michael adducts were formed instead in good yields.10
Aromatic and aliphatic aldehydes smoothly reacted as
second electrophiles to give the adducts as silyl ethers 5
together with a small amount of the parent alcohols 4.
After hydrolysis of the silyl ethers by means of hydro-
chloric acid, the parent alcohols were isolated in fairly
good yields. In each case, observed stereoselectivity was
not satisfactory, in the range of a 1:1–1:2 ratio. The ste-
reochemistry of the major diastereomer of 4aa was deter-
and Development, Ehime University for measurements
of NMR and mass spectra, respectively.
References and notes
1. (a) Omac, J. Application of Organometallic Compounds;
Wiley: Toronto, 1999; Comprehensive Organometallic
Chemistry; 2nd ed; Abel, E. N., Jordon, F., Stone, A.,
Wilkinson, J., Eds.; Pergamon Press: New York, 1995;
Vol. 9 and 12; (b) Brandsma, L.; Vasilevsky, S. F.;
Verkruijsse, H. D. Application of Transition Metal Cata-
lysts in Organic Synthesis; Springer-Verlag: Berlin, Hei-
delberg, New York, 1999.
2. (a) Alonso, F.; Beletskaya, I. P.; Yus, M. Chem. Rev. 2004,
104, 3079–3159; (b) Wicht, D. K.; Glueck, D. S. In
Catalytic Heterofunctionalization; Togni, A., Grutz-
¨
macher, H., Eds.; Wiley-VCH Verlag GmbH: Weinheim,
2001, pp 143–170; (c) Tanaka, M. Top. Curr. Chem. 2004,
232, 25–54.
3. (a) Bunlaksananusorn, T.; Knochel, P. Tetrahedron Lett.
2002, 43, 5817–5819; (b) Shulyupin, M. O.; Kazankova,
M. A.; Beletskaya, I. P. Org. Lett. 2002, 4, 761–763; (c)
Takaki, K.; Koshoji, G.; Komeyama, K.; Takeda, M.;
Shishido, T.; Kitani, A.; Takehira, K. J. Org. Chem. 2003,
68, 6554–6565; (d) Mimeau, D.; Delacroix, O.; Gaumont,
A. C. Chem. Commun. 2003, 2928–2929; (e) Mimeau, D.;
Gaumont, A. C. J. Org. Chem. 2003, 68, 7016–7022; (f)
Hirano, K.; Yorimitsu, H.; Oshima, K. Org. Lett. 2004, 6,
4873–4875; (g) Ohmiya, H.; Yorimitsu, H.; Oshima, K.
Angew. Chem., Int. Ed. 2005, 44, 2368–2370, and refer-
ences cited therein.
4. Hayashi, M.; Matsuura, Y.; Watanabe, Y. Tetrahedron
Lett. 2004, 45, 9167–9169.
5. Silylphosphine 2 did not silylate alcohols without activa-
tion; see Hayashi, M.; Matsuura, Y.; Watanabe, Y.
Tetrahedron Lett. 2004, 45, 1409–1411.
1
mined as anti by H NMR measurement of the cyclic
acetals 9 (from the major isomer) and 90 (from the minor
isomer). When a ketone was applied as a second electro-
phile, the corresponding three-component adduct was
not formed even under more drastic conditions.
R
R'
O
Ph2P
OR
Ph
CO2Et
O
Ph2P
Ph2P
O
6a
t
7a : R = SiMe2 Bu
8a : R = H
9 R = H, R' = Ph
9' R = Ph, R' = H
6. (a) Bordachev, A. A.; Kagachnik, M. M.; Novikova, Z. S.;
Beletskaya, I. P. Izv. Akad. Nauk, Ser. Khim. 1994, 4, 754–
756; (b) Kolodiazhnyi, O. I.; Guliaiko, I. V.; Kolodiazhna,
A. O. Tetrahedron Lett. 2004, 45, 6955–6957.
7. Couret, C.; Escudie, J.; Satge, J.; Anh, N. T.; Soussan, G.
J. Organomet. Chem. 1975, 91, 11–30.
8. Typical procedure: silylphosphine 2 (165 mg, 0.55 mmol)
was added to a stirred mixture of cesium fluoride (4 mg,
0.025 mmol), ethyl acrylate 1a (50 mg, 0.55 mmol) and
benzaldehyde 3a (53 mg, 0.50 mmol) in DMF (3 mL) at rt.
After stirring for 4 h at rt, aqueous hydrochloric acid
(1 M) was added to hydrolyze the silyl ether and the
mixture was extracted twice with CHCl3. The combined
organic extracts were dried, and the solvent was removed
in vacuo. The residue was purified by column chromatog-
raphy on silica gel (eluent: AcOEt/n-hexane = 1/3, Rf 0.40)
affording 4aa (172 mg, 88%) as a mixture of diastereomers
(dr = 1:1.5).4
No trace of three-component coupling product was ob-
served in the reaction of 1a,3a and diphenylphosphine
in the presence of a base;3a the corresponding Michael
adduct 6a (70%) and aldehyde adduct 8a (26%) were
formed instead. This is because of the presence of proton
(diphenylphosphine) which readily quenched the inter-
mediate enolate. The following aldol-type reaction did
not occur under these conditions. More nucleophilic lith-
ium phosphide reacted preferentially with the aldehyde
in comparison to the acrylate, giving 8a (73%) as a main
product together with 6a (13%). Stepwise addition of
ethyl acrylate and benzaldehyde to lithium phosphide
gave 4aa in low yield (38%). From these results, the pres-
ent CsF-catalyzed reaction of silylphosphine is quite suit-
able for this three-component coupling reaction.
In conclusion, we have developed the CsF-catalyzed
reaction of a silylphosphine, Michael acceptors and car-
bonyl compounds to produce multi-functionalized phos-
phines via simultaneous formation of the phosphorus–
carbon and the carbon–carbon bonds. Further study
of the present reaction to improve the stereoselectivity
is now under investigation.
9. Selected data of the products: compound 4ea (dr = 1:1.3);
(major isomer) 1H NMR d 0.87 (t, J = 7.6 Hz, 3H), 1.16 (s,
3H), 1.18–1.30 (m, 2H), 1.40–1.45 (m, 2H), 2.31 (dd,
JP–H = 3.2 Hz, JH–H = 14.0 Hz, 1H), 2.62 (dd, JP–H
1.6 Hz, JH–H = 14.0 Hz, 1H), 3.30 (br d, 1H), 3.75–3.84
(m, 2H), 5.04 (d, J = 2.8 Hz, 1H), 7.24–7.54 (m, 15H); 13
=
C
NMR d 13.7, 18.9 (d, JC–P = 10.8 Hz), 19.2, 30.3, 36.6 (d,
JC–P = 17.2 Hz), 51.2 (d, JC–P = 16.2 Hz), 64.8, 79.4 (d,
JC–P = 8.7 Hz), 127.6, 127.7, 127.8, 128.2 (d, JC–P
=
6.8 Hz), 128.3 (d, JC–P = 6.8 Hz), 128.4, 128.6, 132.8 (d,
JC–P = 12.9 Hz), 133.0 (d, JC–P = 20.1 Hz), 138.7 (d,
JC–P = 38.4 Hz), 139.2 (d, JC–P = 31.1 Hz), 140.0, 175.9
Acknowledgements
1
(d, JC–P = 1.8 Hz); 31P NMR d ꢀ23.0. (minor isomer) H
The authors thank Venture Business Laboratory of
Ehime University and Center for Cooperative Research
NMR d 0.87 (t, J = 7.6 Hz, 3H), 1.15 (s, 3H), 1.18–1.30

5138
M. Hayashi et al. / Tetrahedron Letters 46 (2005) 5135–5138
(m, 2H), 1.40–1.45 (m, 2H), 2.44 (dd, JP–H = 4.0 Hz,
JH–H = 14.4 Hz, 1H), 2.81 (dd, JP–H = 3.2 Hz, JH–H
14.4 Hz, 1H), 3.20 (br, 1H), 3.70–3.82 (m, 2H), 5.02 (br,
1H), 7.24–7.54 (m, 15H); 13C NMR d 13.7, 19.1 (d, JC–P
12.4 Hz), 19.2, 30.3, 34.4 (d, JC–P = 16.6 Hz), 51.6 (d,
JC–P = 16.4 Hz), 64.9, 78.9 (d, JC–P = 7.0 Hz), 127.6, 127.7,
127.8, 128.2 (d, JC–P = 6.6 Hz), 128.3, 128.4 (d,
JC–P = 7.6 Hz), 128.5, 132.8 (d, JC–P = 12.9 Hz), 132.9 (d,
6H), 1.21 (t, J = 7.0 Hz, 3H), 1.89 (m, 1H), 2.29–2.36 (m,
=
2H), 2.74 (m, 1H), 3.63 (m, 1H), 4.01 (m, 2H), 4.83 (d,
J = 4.8 Hz, 1H), 7.22–7.35 (m, 10H); 13C NMR d 14.8,
15.2 (d, JC–P = 17.8 Hz), 19.1, 25.1, 28.1 (d,
JC–P = 14.7 Hz), 49.9 (d, JC–P = 16.6 Hz), 60.9, 75.9 (d,
JC–P = 11.1 Hz), 127.4 (d, JC–P = 19.8 Hz), 127.5 (d,
JC–P = 6.2 Hz), 128.2, 128.7, 132.7 (d, JC–P = 17.8 Hz),
133.6 (d, JC–P = 19.7 Hz), 136.8 (d, JC–P = 13.4 Hz), 137.9
(d, JC–P = 11.7 Hz), 174.1 (d, JC–P = 3.6 Hz); 31P NMR d
ꢀ18.3. IR (neat) 3558, 3022, 2970, 2850, 1604, 1461, 1257,
1133, 1097, 1078, 821, 677 cmꢀ1. Compound 9 (from
major isomer of 4aa) 1H NMR d 1.52 (s, 3H), 1.53 (s, 3H),
1.90 (dd, JP–H = 9.2 Hz, JH–H = 15.5 Hz, 1H), 2.11 (br t,
1H), 2.74 (ddd, JP–H = 10.9 Hz, JH–H = 12.9, 15.5 Hz, 1H),
4.19 (d, J = 12.0 Hz, 1H), 4.22 (d, J = 12.0 Hz, 1H), 5.16
(s,1H), 7.13–7.64 (m, 15H). Compound 90 (from minor
isomer of 4aa) 1H NMR d 1.42 (s, 3H), 1.55 (s, 3H), 1.80–
1.94 (m, 1H), 1.96–2.06 (br, 1H), 2.14–2.32 (m, 1H), 3.86
(t, J = 11.3 Hz, 1H), 4.43 (dd, J = 4.3, 11.3 Hz, 1H), 4.55
(d, J = 10.2 Hz, 1H), 7.18–7.60 (m, 15H).
=
JC–P = 19.9 Hz), 138.7 (d, JC–P = 14.2 Hz), 139.2 (d, JC–P
=
6.2 Hz), 139.8, 175.8 (d, JC–P = 1.1 Hz); 31P NMR d
ꢀ21.4. IR (neat) 3585, 2962, 2877, 1724, 1639, 1454, 1322,
1293, 1164, 1064, 1010, 941, 813, 651 cmꢀ1; FABMS calcd
for C27H31O3P: 434. Found: 435 (M+H). Compound 4ab
1
(major isomer) H NMR d 0.94 (d, J = 5.5 Hz, 6H), 1.21
(t, J = 7.0 Hz, 3H), 1.89 (m, 1H), 2.33–2.44 (m, 2H), 2.74
(m, 1H), 3.55 (m, 1H), 4.01 (m, 2H), 5.04 (d, J = 4.4 Hz,
1H), 7.22–7.35 (m, 10H); 13C NMR d 14.9, 18.9, 21.4, 25.3
(d, JC–P = 12.7 Hz), 34.7 (d, JC–P = 12.5 Hz), 40.1, 60.4,
73.0 (d, JC–P = 10.5 Hz), 127.4 (d, JC–P = 6.7 Hz), 127.6 (d,
JC–P = 7.0 Hz), 127.9, 128.5, 133.3 (d, JC–P = 18.5 Hz),
133.7 (d, JC–P = 18.7 Hz), 137.4 (d, JC–P = 11.0 Hz), 137.8
(d, JC–P = 13.5 Hz), 175.7 (d, JC–P = 3.3 Hz); 31P NMR d
ꢀ19.9. (Minor isomer) 1H NMR d 0.94 (d, J = 5.5 Hz,
10. In some cases using a reactive acceptor like methyl vinyl
ketone, a complex mixture of the products was formed by
multiple addition of the acceptor.