A chemoselective deprotection of trimethylsilyl acetylenes catalyzed by silver salts

Article abstract of DOI:10.1016/j.tetlet.2005.02.017

Trimethylsilyl acetylenes can be selectively deprotected in the presence of a catalytic amount of silver salts. AgNO₃ and AgOTf proved to be the most effective catalyst in a mixture of methanol, water and dichloromethane. Other functional groups, and especially silyl ethers, are not affected in these conditions.

Full text of DOI:10.1016/j.tetlet.2005.02.017

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 2259–2262
A chemoselective deprotection of trimethylsilyl acetylenes
catalyzed by silver salts
*
´ ´
Alban Orsini, Aurelien Viterisi, Anne Bodlenner, Jean-Marc Weibel and Patrick Pale
` ´ ´ ´ ´
Laboratoire de synthese et reactivite organique, associe au CNRS, Institut Le Bel, Universite L. Pasteur, 67000 Strasbourg, France
Received 24 December 2004; revised 31 January 2005; accepted 2 February 2005
Abstract—Trimethylsilyl acetylenes can be selectively deprotected in the presence of a catalytic amount of silver salts. AgNO3 and
AgOTf proved to be the most effective catalyst in a mixture of methanol, water and dichloromethane. Other functional groups, and
especially silyl ethers, are not affected in these conditions.
Ó 2005 Elsevier Ltd. All rights reserved.
R4
R1
Silyl derivatives are widely used as protecting groups for
various functions, mainly hydroxylated ones.1,2 Due to
their increasing use as building blocks for organic based
materials, alkynes have seen a tremendous surge in their
chemistry.3,4 Among other aspects, the protection and
deprotection of terminal alkynes is becoming an impor-
tant issue, especially when selectivity is involved.2c Clas-
sically, such alkynes are protected by silyl groups, which
are removed by fluoride ions in various conditions.5
However, no selectivity with other silyl protecting
groups can be achieved in these deprotection conditions.
Deprotection with excess of mild bases is usually selec-
tive for the less bulky silyl groups (trimethylsilyl TMS
or triethylsilyl TES).2c,5,6
Me3Si
R4
K2CO3 MeOH
Pd(PPh3)4/ AgX cat.
DMF
R1
R2
Ar-I
or
OTf
R2
R3
R3
R4
R1
R3Si
R4
nBu4NF,3H2O
Pd(PPh3)4/ AgX cat.
DMF
R1
R2
OTf
R2
R3
R3
Scheme 1.
ing agent. However, it has to be used in excess (up to
10 equiv) and usually required the presence of excess
potassiumcyanide
Facing such issues while working on the preparation of
conjugated enynes for natural products and organic
materials synthesis,7 we came up with Pd/Ag-catalyzed
cross-coupling procedures selective for 1-trimethylsilyl-
1-alkynes8 and for any 1-trialkylsilyl-1-alkynes9 (Scheme
1).
11a
or pyridine.11b
We found that some silver salts are indeed able to effi-
ciently and selectively catalyze the deprotection of 1-
trimethylsilyl-1-alkynes (Scheme 2) and we present here
our preliminary results.
While deciphering the mechanism of these new coupling
reactions, we observed the key role played by silver
ions10 This led us to investigate further the protiodesilyl-
ation of silylated alkynes using silver salts as deprotect-
ing reagents. To the best of our knowledge, only a few
reports described the use of silver nitrate as a desilylat-
Based on our own experience concerning silver alkynes
and some of our recent results,8–10 we reasoned that in
AgX cat.
R
SiMe3
R
H
CH2Cl2
MeOH-H2O
rt, 2-22h
Keywords: Trimethylsilyl acetylenes; Deprotection; Silver; Catalysis.
*
X=OTf, NO3
Corresponding author. Tel./fax: +33 390 241 517; e-mail: ppale@
chimie.u-strasbg.fr
Scheme 2.
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.02.017

2260
A. Orsini et al. / Tetrahedron Letters 46(2005) 2259–2262
activation. This would lead to cleavage of the C–Si bond
Me3Si
R
and to the in situ formation of an alkynyl silver and a
silyl-X species. In protic solvents, the latter would be
hydrolyzed leading to a better proton source, strong en-
ough to hydrolyze the alkynyl silver species. Silver ion
would thus be released, allowing for a catalytic cycle
to take place (Scheme 3).
Ag
R
ROH
Ag+
_
X
Me3SiX
Me3SiOH
Ag
R
In order to check the above assumptions, we looked at
the behavior of silver chloride, iodide, nitrate, triflate,
and tetrafluoroborate toward 3-trimethylsilyl-2-phenyl
propynol12 1a. Since silver salts and silver acetylides
are not readily soluble in alcohol or water, we selected
various combinations of protic and aprotic solvents
for the deprotection of 1-trimethylsilyl-1-alkynes (Table
1).
HX
R
H
Scheme 3. Mechanistic hypothesis for a Ag-catalyzed deprotection of
1-trimethylsilyl-1-alkynes.
order to achieve deprotection, the silver counter-ion (XÀ
in Scheme 3) of the introduced silver salt must be nucleo-
philic enough to attack the silicon atomupon silver
We were pleased to observe the formation of the
expected terminal alkyne, 2-phenyl propynol 2a but, as
Table 1. Deprotection of 3-trimethylsilyl-2-phenyl propynol 1a in the presence of various silver salts in various conditions
1-TMS-1-Alkyne
Ag salta
Solvent
Time (h)
Yieldb
50
OH
Me2CO
H2O (1 equiv)
1
AgNO3
30
Me3Si
Ph
1a
OH
MeOH 9
H2O 1
2
3
4
AgNO3
AgNO3
AgNO3
30
22
16
30
76
79
Me3Si
Ph
1a
OH
Me2CO 9
H2O 1
Me3Si
Ph
1a
OH
MeOH 4
H2O 1
Me3Si
CH2Cl2
7
Ph
OH
Ph
1a
MeOH 4
H2O 1
5
6
7
8
AgCl
AgI
40
40
40
2.5
50
5
3
Me3Si
CH2Cl2
7
1a
OH
Ph
MeOH 4
H2O 1
Me3Si
CH2Cl2
7
1a
OH
Ph
MeOH 4
H2O 1
AgBF4
AgOTf
—
3
Me3Si
CH2Cl2
7
1a
OH
Ph
MeOH 4
H2O 1
86
0
Me3Si
CH2Cl2
7
1a
OH
Ph
MeOH 4
H2O 1
9
Me3Si
CH2Cl2
7
1a
a 0.1 equiv.
b Yield of isolated pure product.

A. Orsini et al. / Tetrahedron Letters 46(2005) 2259–2262
2261
expected, yields were dramatically influenced by the nat-
ure of both the silver catalyst used (Table 1, entries 4–8)
and the solvents used (Table 1, entries 1–4).
nal alkynes 2b–d, 4e–g, 6b, 8b were obtained in good to
excellent yields (Table 2). As with 1a, the reaction
proved to be more rapid when catalyzed by silver triflate
than by silver nitrate.
In mixtures of methanol and water or acetone and
water, a white precipitate formed upon addition of silver
nitrate. TLC monitoring showed the clean but slow dis-
appearance of the starting material to the benefit of 2a
(entries 1–2). With enough acetone mixed to water, the
reaction mixture appeared cloudy but the reaction was
faster and the deprotected alkyne was recovered in good
yield (entry 3). A homogeneous reaction mixture could
eventually be achieved using a mixture of dichlorometh-
ane, methanol, and water, 7–4–1, respectively. In this
mixture, the deprotection reaction was over after several
hours (entry 4). These results probably reflected the solu-
bility of the alkynyl silver, which should be in situ
formed. Indeed, the presence of silver ion is critical since
no reaction was observed without silver salt whatever
the conditions (e.g., entry 9).
Acetal, ester, and benzyl protecting groups proved to be
perfectly compatible with this method, as demonstrated
by the selective reaction of the pivalate of 5-trimethylsil-
ylpent-4-ynol 3e, its methylethoxymethyl 3f and benzyl
analogs 3g (Table 2, entries 8–13).
More interestingly, this method proved to be selective
toward other silyl protecting groups. Indeed, 3-trimeth-
ylsilyl-2-phenyl propynols O-protected either with tert-
butyldimethylsilyl, tert-butyldiphenylsilyl, or triisoprop-
ylsilyl group, 1b,c,d, were cleanly and selectively
deprotected at the acetylenic end (entries 3–7). A similar
behavior was observed with 5b (entry 14).
The O-tert-butyldimethylsilyl group proved however
sensitive to these conditions after prolonged contact
within the reaction mixture, while bulkier silyl protect-
ing goups (TBDPS, TIPS) remained unaffected. Indeed,
the deprotection of 1b was perfectly selective for the
TMS group up to 7 h but then the O-TBDMS group
started to be removed and was half deprotected after
In order to study the scope of this new deprotection
method, various representative trimethylsilylated alky-
nes 1b–d, 3d–g, 5b, 7b bearing various protecting groups
were then prepared by conventional methods12,13 and
submitted to the above conditions. The expected termi-
Table 2. Deprotection of various 1-trimethylsilyl-1-alkynes: reaction performed with 0.1 equiv of silver salt in a 7-4-1 mixture of CH2Cl2–MeOH–
H2O
1-TMS Alkyne
Catalyst
Time (h)
Yield (%)a
OH
Ph
1
2
AgNO3
AgOTf
16
79
86
Me3Si
1a
2.5
OSitBuMe2
3
4
AgNO3
AgOTf
7.5
4
88
97
Me3Si
1b
Ph
OSitBuPh2
5
AgNO3
2.5
91
1c
Me3Si
Ph
OSiiPr3
6
7
AgNO3
AgOTf
22
96
98b
Me3Si
1d
7.5
Ph
8
9
OMEM
AgNO3
AgOTf
20
9
95
98
3e
Me3Si
10
11
OCOtBu
OBn
AgNO3
AgOTf
22
8
92
95
3f
Me3Si
12
13
AgNO3
AgOTf
22
8
76
97
3g
Me3Si
OSitBuMe2
SiMe3
14
15
AgNO3
AgOTf
5.5
5.5
96b
91b
5b
SiiPr3
16
17
AgNO3
AgOTf
23
7
93b
95
7d
Me3Si
a Yield of isolated pure product.
b Yield relative to conversion, some starting material being recovered.

2262
A. Orsini et al. / Tetrahedron Letters 46(2005) 2259–2262
AgNO3
0.1 eq.
tBuMe2SiO
tBuMe2SiO
Ph
OH
Ph
H
Me3Si
H
CH2Cl2-MeOH
H2O
Ph
1b
2b 2a
Reaction Time:
8h 98 - 2
25h 50 - 50
Scheme 4. Selectivity of the deprotection of 1b.
Kocienski, P. Protecting Groups, 3d ed.; Thieme: Wein-
heim, 2003.
16 h in the presence of 0.1 equiv of silver nitrate (Scheme
4).
2. (a) Lalonde, M.; Chan, T. H. Synthesis 1985, 818–845; (b)
Crouch, R. D.; Nelson, T. D. Synthesis 1996, 1031–
1069; (c) Crouch, R. D. Tetrahedron 2004, 60, 5833–
5871.
3. (a) Caroll, R. L.; Forman, C. B. Angew. Chem., Int. Ed.
2002, 41, 4378–4400; (b) Iwamura, H.; Matsuda, K. In
Modern Acetylene Chemistry; Stang, P. J., Diederich, F.,
Eds.; VCH: Weinheim, 1995; pp 385–414; (c) Young, J.
K.; Moore, J. S. In Modern Acetylene Chemistry; Stang, P.
J., Diederich, F., Eds.; VCH: Weinheim, 1995; pp 416–
442; (d) Diederich, T. In Modern Acetylene Chemistry;
Stang, P. J., Diederich, F., Eds.; VCH: Weinheim, 1995;
pp 443–471.
4. (a) Kraft, A.; Grimsdale, A. C.; Holmes, A. B. Angew.
Chem., Int. Ed. 1998, 37, 402–428; (b) Zhao, Y.; Campbell,
K.; Tykwinski, R. R. J. Org. Chem. 2002, 67, 336–344; (c)
Spreiter, R.; Bosshard, C.; Kno¨pfle, G.; Tykwinski, R. R.;
Schreiber, M.; Diederich, F. J. Phys. Chem. B 1998, 102,
29–32; (d) Schwab, P. F. H.; Noll, B. C.; Michl, J. J. Org.
Chem. 2002, 67, 5476–5485; (f) Zhao, D.; Moore, J. S. J.
Org. Chem. 2002, 67, 3548–3554.
Interestingly enough,
a
complete selectivity was
achieved with a diyne protected with two different silyl
groups (entries 16–17). Indeed, the TMS group of 7d
was removed in the presence of 0.1 equiv of silver nitrate
or triflate, while the TIPS group remained unaffected.
Again, silver triflate induced a faster reaction than the
nitrate (entry 17 vs 16).
In conclusion, we demonstrated here that 1-trimethylsil-
yl-1-alkynes can be selectively deprotected in the pres-
ence of catalytic amounts of silver nitrate or triflate.
Various other protecting groups are fully compatible
with this new method. Interestingly, other silylated func-
tions are not affected by this process. Further works in
this area are now in progress.
Supplementary material
5. Colvin, E. W. Silicon Reagent in Organic Synthesis;
Academic: London, 1988.
6. Benkouider, A.; Pale, P. J. Chem. Res. (S) 1999, 104–
105.
7. (a) Bertus, P.; Pale, P. Tetrahedron Lett. 1996, 37, 2019–
2022; (b) Bertus, P.; Pale, P. Tetrahedron Lett. 1997, 38,
8193–8196; (c) Bertus, P.; Pale, P. J. Organomet. Chem.
1998, 567, 173–180; (d) Halbes, U.; Pale, P. J. Organomet.
Chem. 2003, 687, 420–424.
8. Halbes, U.; Pale, P. Tetrahedron Lett. 2002, 43, 2039–
2042.
9. (a) Halbes, U.; Bertus, P.; Pale, P. Tetrahedron Lett. 2001,
42, 8641–8644; (b) Halbes, U.; Pale, P. Eur. J. Org. Chem.
2002, 2039–2042.
10. (a) Dillinger, S.; Bertus, P.; Pale, P. Org. Lett. 2001, 3,
1661–1664; (b) Halbes, U.; Bertus, P.; Pale, P., in
preparation.
11. (a) Schmidt, H. M.; Arens, J. F. Rec. Trav. Chim. Pays-
Bas 1967, 86, 1138–1142, and for recent exemples; Banfi,
L.; Guanti, G. Eur. J. Org. Chem. 2002, 3745–3755;
Typical procedure for the deprotection of 1-trimethylsil-
yl-1-alkynes catalyzed by silver nitrate or triflate: To a
solution of 1-trimethylsilyl-1-alkyne (1 equiv) in a pre-
mixed mixture of acetone–water–dichloromethane
(4:1:7; 20 mL/mmol) was added silver nitrate or silver
triflate (0.1 equiv). The resulting mixture was then stir-
red at room temperature. Once the starting materials
disappeared, an aqueous saturated solution of ammo-
nium chloride (5 mL/mmol) was added. The resulting
mixture was then extracted three times with dichloro-
methane (5 mL/mmol). The combined organic layers
were dried over MgSO4, filtered, and concentrated in
vacuo. The crude product was purified by silica gel
column chromatography yielding the corresponding
pure 1-alkyne.
Acknowledgements
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The authors thank the CNRS for financial support. A.B.
`
RechercheÕ for a PhD fellowship. We also thank a ref-
eree for pointing out additional references in Ref. 11.
thanks the ÔMinistere de lÕEducation Nationale et de la
12. Cossy, J.; Pale, P. Tetrahedron Lett. 1987, 28, 6039–
6040.
References and notes
13. (a) Brandsma, L. Preparative Acetylenic Chemistry, 2nd
ed.; Elsevier: Amsterdam, 1988; (b) Winterfeldt, E. In
Modern Synthetic Methods; Scheffold, R., Ed.; VCH:
Weinheim, 1992; Vol. 6, pp 103–226.
1. (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in
Organic Synthesis, 2nd ed.; Wiley: New York, 1991; (b)