Copper triflate [Cu(OTf)2] is an efficient and mild catalyst for the silylation of α-hydroxyphosphonates to α-trimethylsilyloxyphosphonates with HMDS at room temperature

Article abstract of DOI:10.1016/S0040-4039(02)02780-6

A broad, adaptable, high yielding and convenient procedure for the fast conversion of various α-hydroxyphosphonates to α-trimethylsilyloxyphosphonates under mild conditions with HMDS in the presence of a catalytic amount of copper triflate is described. T

Full text of DOI:10.1016/S0040-4039(02)02780-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 891–893
Copper triflate [Cu(OTf)2] is an efficient and mild catalyst for
the silylation of a-hydroxyphosphonates to
a-trimethylsilyloxyphosphonates with HMDS at
room temperature
Habib Firouzabadi,* Nasser Iranpoor,* Sara Sobhani, Soheila Ghassamipour and Zohreh Amoozgar
Department of Chemistry, Shiraz University, Shiraz 71454, Iran
Received 28 October 2002; revised 24 November 2002; accepted 6 December 2002
Abstract—A broad, adaptable, high yielding and convenient procedure for the fast conversion of various a-hydroxyphosphonates
to a-trimethylsilyloxyphosphonates under mild conditions with HMDS in the presence of a catalytic amount of copper triflate is
described. This procedure has also been applied successfully for the silylation of alcohols and phenols. © 2003 Elsevier Science
Ltd. All rights reserved.
a-Trimethylsilyloxyphosphonates are fascinating and
versatile compounds in biology, industry and organic
synthesis.1 Having an a-acidic hydrogen they can be
deprotonated with bases such as lithium diisopropyl-
amide.2 This property and also easy cleavage of SiꢀO
and CꢀP bonds in basic and acidic conditions, make
a-carbanionic a-trimethylsilyloxyphosphonates efficient
masked acyl anions.3
ethyl phosphite and trimethylsilyl chloride1b,c as the
most common reagents for preparing a-trimethylsilyl-
oxyphosphonates from their corresponding aldehydes.
The other method for the preparation of these com-
pounds deals with the reaction of silyl phenyl ketones
with trialkylphosphites at 80°C and over a long reac-
tion time (12 h).6 Trimethylsilyl chloride has been used
to prepare diethyl a-trimethylsilyloxybenzylphospho-
nate from the sodium salt of diethyl phosphite and
benzaldehyde in a moderate yield (67%).5b A direct
synthesis of a-trimethylsilyloxyphosphonates from a-
hydroxy phosphonates7 was accomplished by using hex-
amethyldisilathiane at 50–70°C with 55–78% yields.8
a-Lithiated a-trimethylsilyloxyphosphonates react with
various acylating agents to produce the corresponding
a-acylated products, which can be converted to a-
hydroxy ketones after cleavage of the SiꢀO bond and
elimination of dialkyl phosphate in alkaline media.2
They react with various ketones to produce the corre-
sponding a-trimethylsilyloxyketones.4 Carboxylic acids,
unsymmetrical ketones and b,g-unsaturated ketones
can be obtained by alkylation of a-lithiated a-
trimethylsilyloxyphosphonates followed by cleavage of
the SiꢀO bond and elimination of dialkyl phosphate in
alkaline media.5
Manipulation of the hydroxyl functional group of a-
hydroxyphosphonates without affecting SiꢀO and CꢀP
bonds in these molecules is an important synthetic
achievement. We have recently reported mild oxidation
and silylation methods for this aim.9 In our laboratories
we have started an extensive study of new applications
of triflates in organic synthesis. Now we report that
copper triflate10 [Cu(OTf)2] can be used as a mild
A review of the literature showed that the common
methods for the synthesis of a-trimethylsilyloxy phos-
phonates are definitely not easy ones. Harsh reaction
conditions and long reaction times are required for the
reaction of diethyl trimethylsilyloxyphosphite3,5 or tri-
* Corresponding authors. Tel.: +98-711-2284822; fax: +98-711-
2280926 (H.F.); Tel.: +98-711-2284822; fax: +98-711-2280926 (N.I.);
e-mail: firouzabadi@chem.susc.ac.ir; iranpoor@chem.susc.ac.ir
Scheme 1.
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02780-6

892
H. Firouzabadi et al. / Tetrahedron Letters 44 (2003) 891–893
Table 1. Silylation of diethyl a-hydroxyphosphonates (1a–
n) to diethyl a-trimethylsilyloxyphosphonates (2a–n) with
HMDS in the presence of Cu(OTf)2 in CH3CN at room
temperature
phosphonates as the sole products of the reactions were
isolated in excellent yields (90–98%).13
In order to show the unique catalytic behavior of
Cu(OTf)2 in these reactions, we have performed silyla-
tion of 1a with HMDS in the presence of catalytic
Product 2Ref.
R-
Yielda (%)
amounts of LiOTf,14 Ce(OTf)4 as other metal triflates
15
a1a,c,5b,6
b11
c12
C6H5-
97b
90c
95
90
97
95
98
96
91
90c
92
90
91
90
4-CH3C6H4-
4-CH3OC6H4-
2,4,6-(CH3)3C6H2-
2-ClC6H4-
3-ClC6H4-
4-ClC6H4-
2,6-Cl2C6H3-
2-O2NC6H4-
3-O2NC6H4-
4-O2NC6H4-
2-Naphthyl-
3-Pyridyl-
and CuCl2. Production of benzaldehyde in 30–45%
yields was observed which indicates a large amount of
CꢀP bond cleavage in the presence of these catalysts.
d9c
e12
f12
Easy work-up, along with the high yields of the prod-
ucts and also the mildness of the catalyst and the
reaction conditions encouraged us to apply this method
for the protection of hydroxy functional groups in
ordinary alcohols and phenols. Most of the reactions
proceeded smoothly and cleanly in excellent yields in
appropriate reaction times (Table 2).16
g12
h9c
i12
j12
k12
l9c
m9c
n3
PhCHꢁCH-
As shown in Table 2, treatment of a variety of ordinary
alcohols with HMDS in acetonitrile at room tempera-
ture in the presence of catalytic amounts of Cu(OTf)2
gives the corresponding trimethylsilyl ethers in excellent
yields. p-Substituted benzylic alcohols containing elec-
tron-donating and electron-withdrawing groups, pri-
mary and secondary aliphatic alcohols were protected
efficiently in short reaction times (entries 1–12). Longer
reaction times are required for complete conversion of
allylic and tertiary aliphatic alcohols to the correspond-
ing silylated products (entries 13–18). p-Cresol was
silylated faster with higher yield than phenol (entries
19, 20). While even after 24 h stirring, conversion of
a Isolated yields, reaction time=15 min. The amount of copper
triflate and HMDS were 0.12 and 0.7 equiv., respectively.
b The amount of copper triflate was 0.11 equiv.
c The amount of HMDS was 1 equiv.
catalyst for the activation of HMDS to affect efficient
silylation of various types of diethyl a-hydroxyphos-
phonates (1a–n). The reactions proceeded smoothly and
effortlessly in a few minutes in CH3CN at room tem-
perature (Scheme 1, Table 1).
In all these reactions cleavage of CꢀP and SiꢀO bonds
was not observed and only diethyl a-trimethylsilyloxy
Table 2. Silylation of alcohols and phenols to trimethyl silyl ethers with HMDS in the presence of Cu(OTf)2 in CH3CN at
room temperature
Entry
Substrate
Time (min)
Yieldsa (%)
1
2
3
4
5
6
7
8
C6H5CH2OH
5
5
15
35
57
25
30
5
40
35
40
75
65
95b
90b
95b
90b
95c
98c
91c
95c
95b
98b
98c
99b
90b
85b
93c
90c
91c
93c
70c
85c
4-CH3C6H4CH2OH
4-CH3OC6H4CH2OH
4-ClC6H4CH2OH
Anthracene-9-methanol
Ph(CH2)2CH2OH
CH3(CH2)6CH2OH
PhCH2CH2OH
9
PhCH(C2H5)OH
(Ph)2CHOH
10
11
12
13
14
15
16
17
18
19
20
21
22
CH3(CH2)5CH(CH3)OH
2-(6,6-Dimethylbicyclo[3.1.1]hept-2-ene-2-yl)ethanol
CH3(CH2)5CH(CHꢁCH2)OH
(CH3)2CꢁCHCH2OH
a-Terpineol
5-CH3-5-decanol
1-Adamantanol
CH3CH2C(CH3)2OH
C6H5OH
4-CH3C6H4OH
80
24 h
19 h
120
150
120
5
d
4-O2NC6H4OH
4-AcetylC6H4OH
24 h
24 h
–
d
–
a Isolated yields.
b The equivalent ratio of substrate/HMDS/Cu(OTf)2 is 1/0.5/0.01.
c The equivalent ratio of substrate/HMDS/Cu(OTf)2 is 1/0.7/0.01.
d No reaction.

H. Firouzabadi et al. / Tetrahedron Letters 44 (2003) 891–893
893
phenols with electron-withdrawing groups to the corre-
sponding trimethylsilyl ethers was not observed under
similar reaction conditions (entries 21 and 22).
7. (a) Baraldi, P. G.; Guarneri, M.; Moroder, F.; Polloni,
G. P.; Simoni, D. Synthesis 1982, 653–655; (b) Sardarian,
A. R.; Kaboudin, B. Synth. Commun. 1997, 27, 543–551;
(c) Texier-Boullet, F.; Foucaud, A. Synthesis 1982, 916.
8. Lebedev, E. P.; Mizhiritskii, M. D.; Baburina, V. A.;
Mironov, V. F.; Ofitserov, E. N. Zh. Obshch. Khim. 1979,
49, 1731–1737.
9. (a) Firouzabadi, H.; Iranpoor, N.; Sobhani, S.; Sardar-
ian, A. R. Tetrahedron Lett. 2001, 42, 4369–4371; (b)
Firouzabadi, H.; Iranpoor, N.; Sobhani, S. Tetrahedron
Lett. 2002, 43, 477–480; (c) Firouzabadi, H.; Iranpoor,
N.; Sobhani, S. Tetrahedron Lett. 2002, 43, 3653–3655.
10. Jenkins, C. L.; Kochi, J. K. J. Am. Chem. Soc. 1972, 94,
843–855.
In conclusion, in this study we have found that
Cu(OTf)2 is a mild and suitable catalyst for the activa-
tion of HMDS to silylate hydroxy functional groups of
structurally different a-hydroxyphosphonates under
mild reaction conditions with excellent yields and with-
out cleavage of CꢀP bonds. We have also applied this
protocol for the efficient silylation of ordinary alcohols
and phenols.
11. Ernst, A.; Karola, H.; Hermann, M. Synthesis 1990,
323–326.
Acknowledgements
12. Yongzhen, Z.; Zhonghua, L. Yingyong Huaxue 1991, 8,
33–37.
We are thankful to the Shiraz University Research
Council for the partial support of this work.
13. Typical procedure for the preparation of diethyl h-
trimethylsilyloxyphosphonates from diethyl h-hydroxy-
phosphonates catalyzed by copper triflate [Cu(OTf )2]: A
solution of 1a (1 mmol, 0.244 g) and HMDS (0.7 mmol)
was prepared in CH3CN (5 mL). Cu(OTf)2 (0.11 mmol)
was added to the mixture at room temperature. After 15
min dichloromethane (10 mL) was added to the reaction
mixture and it was washed with H2O (3×10 mL). The
organic layer was separated and dried over anhydrous
sodium sulfate. After evaporation of the solvent, the
highly pure product 2a was obtained in 97% yield.
14. Firouzabadi, H.; Iranpoor, N.; Eslami, Sh. Tetrahedron
Lett. 1999, 40, 4055–4058.
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