Facile deprotection of bulky (trialkylsilyl)acetylenes with silver fluoride

Article abstract of DOI:10.1055/s-0029-1216788

An efficient and mild method is developed for the deprotection of bulky (trialkylsilyl)acetylenes. Treatment of 1-(triisopropylsilyl) acetylenes with silver fluoride, followed by hydrolysis of the intermediate silver acetylide with organic or inorganic ac

Full text of DOI:10.1055/s-0029-1216788

PAPER
1963
Facile Deprotection of Bulky (Trialkylsilyl)acetylenes with Silver Fluoride
F
acile Deprote
a
ction of Bu
n
lky (Trialky
g
lsilyl)acetyle
h
nes ee Kim,* Bogyeong Kim, Jinkyung In
College of Pharmacy, Seoul National University, San 56-1, Shilim, Kwanak, Seoul 151-742, Korea
Fax +82(2)8880649; E-mail: pennkim@snu.ac.kr
Received 13 January 2009; revised 12 February 2009
yield (Scheme 1).7a Our attempts to desilylate the corre-
sponding TIPS-protected acetylene 3 using the silver ni-
trate- or silver triflate-mediated conditions led to the
recovery of only starting material. This failure could be
Abstract: An efficient and mild method is developed for the depro-
tection of bulky (trialkylsilyl)acetylenes. Treatment of 1-(triisopro-
pylsilyl)acetylenes with silver fluoride, followed by hydrolysis of
the intermediate silver acetylide with organic or inorganic acids,
produces terminal acetylenes in good to excellent yields. The attributed to the increased stability of the bulkier silyl
reactions are chemoselective and various functional groups are
group.
tolerated.
Key words: desilylation, trialkylsilyl, silver fluoride, chemoselec-
tivity, alkynes
BnO
BnO
ref. 7a
1
TMS
AgNO3
BnO
or AgOTf
2
H
Terminal alkynes are frequently masked with a trialkylsi-
lyl group during multistep organic synthesis. Typically,
less-bulky trialkylsilyl groups, such as trimethylsilyl
(TMS) or triethylsilyl (TES), are used as the protecting
groups for terminal alkynes.1 On the other hand, relatively
bulkier trialkylsilyl protecting groups, for example, triiso-
propylsilyl (TIPS), are also synthetically useful since the
more sterically hindered C–C triple bonds and C–Si single
bonds are inert to a variety of reagents.2
X
3
TIPS
Scheme 1
alkynes
Silver salt mediated deprotection of TMS-protected
For efficient removal of the bulky triisopropylsilyl pro-
tecting group we chose to use silver fluoride. In previous
investigations we developed the silver fluoride mediated
in situ desilylative–bromination of various alkynylsilanes,
including TIPS-protected alkynes.8 Based on our own ex-
perience and the observations of others,9,10 a silver acetyl-
ide intermediate such as 4 is considered to be involved in
this halogenation reaction, as shown in Scheme 2. We en-
visioned that hydrolysis of the presumed silver acetylide
intermediate 4 would produce the terminal alkyne 5, thus
providing a mild and efficient method for the deprotection
of (triisopropylsilyl)acetylenes.
Although many procedures are available for the deprotec-
tion of TMS-protected alkynes,1,3 only a few methods
have been reported for the deprotection of bulkier TIPS-
protected alkynes.1,4 The typical reagent used to cleave
TIPS-protected alkynes is tetrabutylammonium fluoride.
Unfortunately, silyl deprotection reactions using tetrabu-
tylammonium fluoride often require excess of the reagent
and suffer somewhat from its inherent basic properties.5
Hence, there is still a requirement for alternative and effi-
cient methods for the deprotection of TIPS-protected
alkynes.
F–
Ag+
AgF
R
SiiPr3
R
SiiPr3
Silver salts have been utilized as mild reagents for depro-
tecting TMS-alkynes. Treatment of TMS-protected
alkynes with a large excess of silver nitrate followed by
addition of a large excess of aqueous potassium cyanide
provides the corresponding deprotected terminal alkyne.6
Two research groups have reported independently the cat-
alytic versions of this reaction which do not require the
use of cyanide.7 Silver nitrate and silver triflate were ob-
served to be effective catalysts under semi-aqueous or al-
coholic conditions. However, these conditions were only
effective for TMS-protected acetylenes and not for bulki-
er (trialkylsilyl)acetylenes. For example, the trimethylsi-
lyl group of alkyne 1 was removed successfully in the
presence of silver nitrate or silver triflate to give 2 in high
AgF, NBS
MeCN, r.t.
ref. 8
Br+
R
Br
R
Ag
H
4
H+
R
5
Scheme 2 Desilylative–bromination of alkynylsilanes and hydro-
lysis of the proposed silver acetylide intermediate
To test the feasibility of our deprotection approach we
conducted initial studies with (triisopropylsilyl)acetylene
3 (Table 1). A solution of 3 in acetonitrile was treated with
a slight excess (1.5 equivalents) of silver fluoride at room
temperature, and the reaction stirred for three hours. Thin
SYNTHESIS 2009, No. 12, pp 1963–1968
x
x.
x
x
.
2
0
0
9
Advanced online publication: 30.04.2009
DOI: 10.1055/s-0029-1216788; Art ID: F01709SS
© Georg Thieme Verlag Stuttgart · New York

1964
S. Kim et al.
PAPER
layer chromatography showed complete disappearance of
the starting material and the formation of a polar compo-
nent, which was presumed to be the intermediate silver
acetylide. In order to hydrolyze the silver acetylide we
tested several acids. Formation of terminal acetylene 2
was achieved by the addition of two equivalents or greater
of aqueous hydrochloric acid (1 M) to the reaction mix-
ture (entry 1). After 5 minutes, thin layer chromatography
indicated complete consumption of the polar material and
work-up, followed by column chromatography, afforded
a very high yield of deprotected alkyne 2 (92%). When the
same reaction mixture was treated with two equivalents of
an organic acid, such as p-toluenesulfonic acid (TsOH) or
trifluoroacetic acid (TFA), similar results were observed
(entries 2–3). When the hydrolysis was attempted using
saturated aqueous ammonium chloride solution, the reac-
tion was slow, but after 90 minutes at room temperature,
a good yield of product 2 was obtained (entry 4).
Table 1 Optimization of the Reaction Conditions for the Deprotec-
tion of Alkyne 3
i) AgF (1.5 equiv)
solvent, r.t.
BnO
BnO
ii) acid, r.t.
one-pot
3
2
TIPS
H
Entry
Solvent
MeCN
MeCN
MeCN
MeCN
DMF
Acid
Time (min) Yield (%)a
1
2
3
4
5
6
7
8
9
1 M HCl
TsOH
TFA
5
5
92
92
93
89
94
93
5
sat. NH4Cl
1 M HCl
1 M HCl
–
90
5
MeOH
Me2CO
THF
5
b
–
–
b
We next examined the effect of solvents on the deprotec-
tion reaction. The desilylation occurred equally well in
N,N-dimethylformamide and methanol (entries 5–6), pro-
ducing similar results to those obtained using acetonitrile.
However, the use of acetone, tetrahydrofuran or dichlo-
romethane as solvent did not yield the desired product,
presumably as a result of the low solubility of silver fluo-
ride in these solvents (entries 7–9).
–
–
–
b
CH2Cl2
–
–
–
a Yield refers to pure isolated product.
b Product not detected.
Table 2 Deprotection of TIPS-Protected Acetylenes with Silver Fluoride
i) AgF, MeCN, r.t., 3 h
R
H
R
TIPS
ii) 1 N HCl, r.t., 5 min
one-pot
Entry
1
Substrate
Product
Yield (%)a
92
BzO
PvO
AcO
BzO
PvO
AcO
TrO
6
7
14
TIPS
TIPS
TIPS
TIPS
H
H
2
15
16
17
86
3
8
9
96
7
7
H
H
4b
80 (91)c
TrO
O
OH
OH
5
6
10
11
18
19
94
92
O
NBoc
NBoc
TIPS
H
TIPS
H
HO
HO
H
H
TIPS
TBS
7
8
12
13
20
2
97
93
BnO
BnO
BnO
BnO
a Yield refers to pure isolated product.
b DMF was used as the solvent.
c Isolated yield after hydrolysis with sat. aq NH4Cl.
Synthesis 2009, No. 12, 1963–1968 © Thieme Stuttgart · New York

PAPER
Facile Deprotection of Bulky (Trialkylsilyl)acetylenes
1965
were obtained on a Jasco FT/IR-4200 spectrophotometer. 1H NMR
(400 or 300 MHz) and 13C NMR (100 or 75 MHz) spectra were re-
corded in ppm relative to the non-deuterated solvent as an internal
reference using a Jeol JNM-LA 300 or a Bruker FT-NMR Avance
300 spectrometer. Low-resolution and high-resolution mass spectra
(HRMS) were recorded using electron impact (EI), fast atom bom-
bardment (FAB) or chemical ionization (CI) on a Jeol JMS-700
GC-MS or a Jeol JMS-600W spectrometer. Melting points were
measured with a Büchi B-540 apparatus and are uncorrected.
Reaction of 3 with other inorganic fluoride sources, name-
ly lithium fluoride, cesium fluoride, aluminum fluoride
and sodium fluoride in acetonitrile led to recovery of only
unreacted starting material. These results imply that both
coordination of silver to the alkyne and the high silico-
philic properties of fluoride ions are required for the desi-
lylation of bulky (trialkylsilyl)acetylenes.
To explore the scope of this transformation, we examined
several terminal silyl-protected alkynes as substrates. Tri-
isopropylsilyl-protected acetylenes bearing various func-
tional groups were deprotected using silver fluoride (1.5
equivalents) in acetonitrile at room temperature. Hydroly-
sis of the silver acetylide intermediate was achieved by
the addition of excess hydrochloric acid (1 M). The corre-
sponding terminal acetylenes were obtained in good to ex-
cellent yields and the results are summarized in Table 2.
[5-(Benzyloxy)pent-1-ynyl]triisopropylsilane (3)
To a soln of [(pent-4-yn-1-yloxy)methyl]benzene (2)11 (1.56 g, 8.95
mmol) in THF (30 mL) was slowly added n-BuLi (7.27 mL, 11.6
mmol, 1.6 M soln in hexanes) at –78 °C. The reaction mixture was
stirred for 10 min at r.t. and TIPSCl (2.35 mL, 10.7 mmol) was add-
ed at –78 °C. The resulting mixture was warmed to r.t. and stirred
for 2 h after which sat. NH4Cl soln (50 mL) was added. The aq layer
was extracted with Et2O (2 × 50 mL) and the combined organic lay-
er was washed with brine (50 mL), dried over MgSO4, filtered and
concentrated. The residue was purified by column chromatography
on silica gel (hexane–EtOAc, 20:1) to give 3 as a colorless oil;
yield: 4.45 g (92%).
This method is compatible with base-sensitive functional
groups such as benzoate, pivaloate and acetate (Table 2,
entries 1–3). Acid-sensitive functional groups such as tri-
tyl ether (entry 4) and N-Boc-N,O-acetal (entry 5) were
also tolerated. (Triisopropylsilyl)acetylenes 10 and 11,
which contain a free hydroxy group, were also deprotect-
ed smoothly (entries 5–6). The TIPS-protected diyne 12
was efficiently converted into the corresponding terminal
diyne (entry 7). Under the same reaction conditions, the
bulky tert-butyldimethylsilyl (TBS) group, was also re-
moved in very high yield (entry 8).
IR (CHCl3): 2941, 2863, 2171, 1462, 1109 cm–1.
1H NMR (CDCl3, 400 MHz): d = 0.95–1.13 (m, 21 H), 1.89 (quin,
J = 6.5 Hz, 2 H), 2.44 (t, J = 6.9 Hz, 2 H), 3.65 (t, J = 6.2 Hz, 2 H),
4.56 (s, 2 H), 7.30–7.39 (m, 5 H).
13C NMR (CDCl3, 100 MHz): d = 11.1 (3 C), 16.5, 18.5 (6 C), 29.0,
68.6, 72.9, 80.2, 108.2, 127.3, 127.4 (2 C), 128.1 (2 C), 138.4.
MS (CI): m/z (%) = 329 (17) [M – H+], 311 (7), 287 (71), 245 (14).
HRMS (CI): m/z [M – H+] calcd for C21H33OSi: 329.2301; found:
329.2300.
Interestingly, this silver fluoride–acid reaction system is
chemoselective (Scheme 3). TIPS-protected acetylenes
21 and 22, which also contain TIPS-protected hydroxy
groups, formed the corresponding terminal acetylenes 23
and 24, respectively, in excellent yields, without any sig-
nificant O-silyl group removal.
(2E)-(5-Triisopropylsilyl)pent-2-en-4-yn-1-yl Benzoate (6)
To a soln of 5-(triisopropylsilyl)penta-2,4-diyn-1-ol12 (400 mg,
3.38 mmol) in THF (10 mL) at –78 °C was slowly added LiAlH4
(4.65 mL, 4.65 mmol, 1.0 M soln in THF). The reaction mixture was
allowed to warm to r.t. with stirring for 1 h. Next, H2O (4.6 mL),
10% aq NaOH soln (4.6 mL) and H2O (4.6 mL) were added sequen-
tially. The resulting mixture was filtered through a glass funnel
packed with Celite. The filtrate was extracted with EtOAc (2 × 20
mL), washed with brine (20 mL), dried over Na2SO4 and concen-
trated. The residue was purified by column chromatography on sil-
ica gel (hexane–EtOAc, 4:1) to give (2E)-5-(triisopropylsilyl)pent-
2-en-4-yn-1-ol as a colorless oil; yield: 370 mg (92%).
TIPSO
i, ii
TIPSO
21
23
TIPS
90%
H
TIPSO
TIPSO
i, ii
94%
IR (CHCl3): 3334, 2943, 2866, 2131, 1463 cm–1.
22
24
TIPS
H
1H NMR (CDCl3, 300 MHz): d = 1.01–1.15 (m, 21 H), 4.21 (dd,
J = 5.4, 1.8 Hz, 2 H), 5.80 (td, J = 15.9, 1.8 Hz, 1 H), 6.31 (td,
J = 15.9, 5.1 Hz, 1 H).
Scheme 3 Reagents and conditions: i) AgF, MeOH, r.t., 3 h; ii) 1 M
HCl, r.t., 5 min
13C NMR (CDCl3, 75 MHz): d = 11.2 (3 C), 18.5 (6 C), 62.7, 91.5,
104.8, 110.7, 142.5.
MS (EI): m/z (%) = 238 (7) [M+], 195 (100), 167 (20), 125 (25).
HRMS (EI): m/z [M+] calcd for C14H26OSi: 238.1753; found:
In conclusion, we have developed an efficient and mild
method for the deprotection of 1-(triisopropylsilyl)acety-
lenes. Treatment of TIPS-protected acetylenes with silver
fluoride, followed by hydrolysis of the silver acetylide in-
termediate with organic or inorganic acids, produced the
corresponding terminal acetylenes in good to excellent
yields. Various functional groups including, triisopropyl-
silyl ethers, are tolerated under the reported conditions.
238.1753.
To a soln of (2E)-5-(triisopropylsilyl)pent-2-en-4-yn-1-ol (150 mg,
0.62 mmol) in pyridine (6 mL) was added benzoyl chloride (0.08
mL, 0.74 mmol) at 0 °C. The reaction mixture was stirred at r.t. for
1 h, after which the mixture was quenched with H2O (10 mL) and
extracted with EtOAc (2 × 15 mL). The combined organic layer was
washed with brine (20 mL), dried over MgSO4 and concentrated.
The residue was purified by column chromatography on silica gel
(hexane–EtOAc, 20:1) to give 6 as a colorless oil; yield: 180 mg
(84%).
All chemicals were reagent grade and used as purchased. Reactions
were performed under an inert atmosphere of dry Ar or N2 using dis-
tilled dry solvent. Reactions were monitored by TLC using Merck
silica gel 60 F-254 thin layer plates. Flash column chromatography
was carried out on Merck silica gel 60 (230–400 mesh). IR spectra
IR (CHCl3): 2942, 2864, 1725, 1267, 710 cm–1.
Synthesis 2009, No. 12, 1963–1968 © Thieme Stuttgart · New York

1966
S. Kim et al.
PAPER
1H NMR (300 MHz, CDCl3): d = 0.97–1.12 (m, 21 H), 4.77 (d,
J = 6.0 Hz, 2 H), 5.83 (d, J = 15.9 Hz, 1 H), 6.26 (td, J = 15.9, 5.7
Hz, 1 H), 7.34 (t, J = 7.8 Hz, 2 H), 7.40–7.49 (m, 1 H), 7.98 (d,
J = 7.2 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 11.1 (3 C), 18.5 (6 C), 64.1, 76.6,
92.5, 104.2, 113.5, 128.3 (2 C), 129.6 (2 C), 133.0, 137.1, 165.8.
tography on silica gel (hexane–EtOAc, 10:1) to give 8 as a colorless
oil; yield: 150 mg (85%).
IR (CHCl3): 2936, 2863, 2170, 1743, 1239 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.94–1.03 (m, 21 H), 1.25 (br s, 8
H), 1.37 (br s, 2 H), 1.47 (quin, J = 6.7 Hz, 2 H), 1.57 (quin, J = 6.9
Hz, 2 H), 1.99 (s, 3 H), 2.19 (t, J = 6.8 Hz, 2 H), 4.00 (t, J = 6.7 Hz,
2 H).
MS (FAB): m/z (%) = 343 (17) [M + H+], 299 (25), 257 (13), 235
(100), 157 (32).
13C NMR (100 MHz, CDCl3): d = 11.5 (3 C), 18.5 (6 C), 19.7, 20.9,
25.8, 28.5 (2 C), 28.7, 28.9, 29.1, 64.5, 79.9, 109.1, 171.0.
HRMS (FAB): m/z [M + H+] calcd for C21H31O2Si: 343.2093;
found: 343.2074.
MS (CI): m/z (%) = 368 (11), 367 (38) [M + H]+, 325 (30), 323
(100), 173 (10).
5-(Triisopropylsilyl)pent-4-yn-1-yl Pivalate (7)
HRMS (CI): m/z [M + H+] calcd for C22H43O2Si: 367.3032; found:
367.3031.
To a soln of pent-4-yn-1-yl pivalate (15)7 (390 mg, 2.31 mmol) in
THF (20 mL) was slowly added n-BuLi (1.73 mL, 2.77 mmol, 1.6
M soln in hexanes) at –78 °C. The reaction mixture was stirred for
10 min at r.t. and then TIPSCl (0.59 mL, 2.77 mmol) was added at
–78 °C. The mixture was warmed to r.t. and stirred for 2 h. The re-
action was quenched with sat. NH4Cl soln (30 mL) and extracted
with Et2O (2 × 30 mL). The combined organic layer was washed
with brine (20 mL), dried over MgSO4, filtered and concentrated.
The residue was purified by column chromatography on silica gel
(hexane–EtOAc, 15:1) to give 7 as a pale yellow oil; yield: 650 mg
(87%).
Triisopropyl[5-(trityloxy)pent-1-yn-1-yl]silane (9)
To a soln of [(pent-4-yn-1-yloxy)methanetriyl]tribenzene (17)13
(344 mg, 1.05 mmol) in THF (5 mL) was slowly added n-BuLi
(0.78 mL, 1.26 mmol, 1.6 M soln in hexanes) at –78 °C. The reac-
tion mixture was stirred for 10 min at r.t. and then TIPSCl (0.270
mL, 1.26 mmol) was added at –78 °C. The mixture was warmed to
r.t. and then stirred for 2 h. The resulting mixture was quenched
with sat. NH4Cl soln (10 mL) and extracted with Et2O (2 × 20 mL).
The combined organic layer was washed with brine (20 mL), dried
over MgSO4, filtered and concentrated. The residue was purified by
column chromatography on silica gel (hexane–EtOAc, 30:1) to give
9 as a white solid; yield: 392 mg (77%); mp 72–74 °C.
IR (CHCl3): 2942, 2865, 2173, 1733, 1155 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.94–1.03 (m, 21 H), 1.16 (s, 9 H),
1.81 (quin, J = 6.6 Hz, 2 H), 2.31 (t, J = 7.1 Hz, 2 H), 4.12 (t, J = 6.2
Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = 11.1 (3 C), 16.4, 18.5 (6 C), 27.1
(3 C), 27.8, 38.6, 62.7, 81.0, 107.2, 178.2.
IR (CHCl3): 2941, 2863, 2172, 1449, 1073 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.96–1.07 (m, 21 H) 1.89 (quin,
J = 6.9 Hz, 2 H), 2.41 (t, J = 6.9 Hz, 2 H), 3.21 (t, J = 6.6 Hz, 2 H),
7.22–7.33 (m, 10 H), 7.45–7.50 (m, 5 H).
MS (FAB): m/z (%) = 325 (29) [M + H]+, 281 (77), 215 (100), 157
(18), 57 (75).
13C NMR (75 MHz, CDCl3): d = 11.1 (3 C), 14.1, 18.5 (6 C), 29.5,
62.4, 80.2, 86.3, 108.4, 126.8 (3 C), 127.6 (6 C), 128.6 (6 C), 144.3
(3 C).
HRMS (FAB): m/z [M + H+] calcd for C19H37O2Si: 325.2563;
found: 325.2573.
MS (CI): m/z (%) = 482 (35) [M+], 241 (100), 157 (32), 84 (17).
HRMS (CI): m/z [M + H+] calcd for C33H43OSi: 483.3083; found:
11-(Triisopropylsilyl)undec-10-yn-1-yl Acetate (8)
To a soln of undec-10-yn-1-ol (800 mg, 4.75 mmol) in THF (16 mL)
was slowly added EtMgBr (12.35 mL, 12.35 mmol, 1.0 M soln in
THF) at 0 °C. The reaction mixture was stirred overnight at r.t. and
then TIPSCl (2.64 mL, 12.35 mmol) was added at 0 °C. The mixture
was heated at 40 °C for 5 h, then cooled to r.t., quenched with sat.
NH4Cl soln (10 mL) and diluted with EtOAc (20 mL). The organic
layer was washed with brine (20 mL), dried over MgSO4, filtered
and concentrated in vacuo. The residue was purified by column
chromatography on silica gel (hexane–EtOAc, 4:1) to give 11-(tri-
isopropylsilyl)undec-10-yn-1-ol as a pale yellow oil; yield: 1.18 g
(77%).
483.3000.
tert-Butyl (4S)-4-[(1R)-1-Hydroxy-3-(triisopropylsilyl)prop-2-
yn-1-yl]-2,2-dimethyloxazolidine-3-carboxylate (10)14
Spectroscopic data were identical to those reported.
1H NMR (300 MHz, CDCl3, mixture of rotamers): d = 1.01 (s, 21
H), 1.36–1.59 (m, 15 H), 3.87–4.05 (m, 2 H), 4.48–4.62 (m, 2 H).
[4-(Triisopropylsilylethynyl)phenyl]methanol (11)8a
Spectroscopic data were identical to those reported.
IR (CHCl3): 3334, 2931, 2863, 2171, 1463 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.13 (s, 21 H), 1.73 (t, J = 5.7 Hz,
1 H), 4.69 (d, J = 5.7 Hz, 2 H), 7.30 (d, J = 8.4 Hz, 2 H), 7.47 (d,
J = 8.4 Hz, 2 H).
1H NMR (400 MHz, CDCl3): d = 0.97–1.01 (m, 21 H), 1.24–1.32
(m, 8 H), 1.36–1.38 (m, 2 H), 1.43–1.51 (m, 4 H), 2.11 (br s, 1 H),
2.18 (t, J = 6.7 Hz, 2 H), 3.56 (t, J = 6.6 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 11.5 (3 C), 18.5 (6 C), 19.7, 25.6,
28.5, 28.7, 28.9, 29.1, 29.3, 29.4, 32.6, 62.7, 79.8, 109.1.
MS (CI): m/z (%) = 326 (15), 325 (45) [M + H]+, 323 (13), 281
(100), 157 (39).
[5-(Benzyloxy)penta-1,3-diyn-1-yl]triisopropylsilane (12)8
Spectroscopic data were identical to those reported.
1H NMR (300 MHz, CDCl3): d = 1.11 (s, 21 H), 4.25 (s, 2 H), 4.62
(s, 2 H), 7.31–7.38 (m, 5 H).
HRMS (CI): m/z [M + H+] calcd for C20H41OSi: 325.2927; found:
325.2931.
[5-(Benzyloxy)pent-1-yn-1-yl](tert-butyl)dimethylsilane (13)
To a soln of [(pent-4-yn-1-yloxy)methyl]benzene (2)11 (448 mg,
2.57 mmol) in THF (20 mL) was slowly added n-BuLi (1.93 mL,
3.08 mmol, 1.6 M soln in hexanes) at –78 °C. The reaction mixture
was stirred for 10 min at r.t. and then TBDMSCl (465 mg, 3.08
mmol) was added at –78 °C. The mixture was warmed to r.t. and
stirred for 2 h. The resulting mixture was quenched with sat. NH4Cl
soln (20 mL) and the aqueous layer extracted with Et2O (2 × 25
To a soln of 11-(triisopropylsilyl)undec-10-yn-1-ol (158 mg, 0.480
mmol) in pyridine (2.4 mL) and Ac2O (0.140 mL, 1.44 mmol) was
added DMAP (3.00 mg, 0.019 mmol). After stirring at r.t. for 30
min the reaction mixture was diluted with toluene (15 mL) and then
concentrated in vacuo. The residue was purified by column chroma-
Synthesis 2009, No. 12, 1963–1968 © Thieme Stuttgart · New York

PAPER
Facile Deprotection of Bulky (Trialkylsilyl)acetylenes
IR (CHCl3): 3295, 3030, 2927, 2858, 1106 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.75 (quin, J = 6.5 Hz, 2 H), 1.86
(dt, J = 2.5, 0.5 Hz, 1 H), 2.24 (dt, J = 6.9, 2.5 Hz, 2 H), 3.50 (t,
J = 6.3 Hz, 2 H), 4.44 (s, 2 H), 7.17–7.30 (m, 5 H).
13C NMR (100 MHz, CDCl3): d = 14.9, 28.3, 68.2, 68.4, 72.5, 83.5,
127.1, 127.2 (2 C), 128.0 (2 C), 138.2.
MS (CI): m/z (%) = 174 (31), 173 (100) [M – H]+, 157 (10), 97 (14).
HRMS (CI): m/z [M – H+] calcd for C12H13O: 173.0966; found:
1967
mL). The combined organic layer was washed with brine (30 mL),
dried over MgSO4, filtered and concentrated. The residue was puri-
fied by column chromatography on silica gel (hexane–EtOAc, 20:1)
to give 13 as a colorless oil; yield: 619 mg (83%).
IR (CHCl3): 2952, 2929, 2856, 2173, 1108 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.12 (s, 6 H), 0.96 (s, 9 H) 1.86
(quin, J = 6.9 Hz, 2 H), 2.40 (t, J = 7.2 Hz, 2 H), 3.61 (t, J = 6.0 Hz,
2 H), 4.54 (s, 2 H), 7.25–7.38 (m, 5 H).
13C NMR (75 MHz, CDCl3): d = –4.5 (2 C), 16.4, 16.6 (3 C), 26.0,
28.8, 68.6, 72.9, 82.6, 107.1, 127.45 (2 C), 127.49, 128.2 (2 C),
138.4.
MS (CI): m/z (%) = 289 (100) [M + H]+, 288 (13), 287 (52), 273
(36), 231 (94).
HRMS (CI): m/z [M + H+] calcd for C18H29OSi: 289.2982; found:
289.2980.
173.0966.
(2E)-Pent-2-en-4-yn-1-yl Benzoate (14)
Starting from 6 (67.0 mg, 0.190 mmol), compound 14 was isolated
as a colorless oil (eluent: hexane–EtOAc, 15:1); yield: 34 mg
(92%).
IR (CHCl3): 3301, 2942, 2865, 1462, 1093 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.92 (d, J = 2.5 Hz, 1 H), 4.84 (dd,
J = 7.1, 1.7 Hz, 2 H), 5.81 (dd, J = 19.9, 2.3 Hz, 1 H), 6.36 (td,
J = 20.0, 7.1 Hz, 1 H), 7.42 (t, J = 9.7 Hz, 2 H), 7.55 (t, J = 9.3 Hz,
1 H), 8.03 (d, J = 9.1 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 63.9, 78.7, 80.9, 112.1, 128.1 (2
C), 129.6 (2 C), 129.7, 133.1, 138.3, 165.9.
MS (CI): m/z (%) = 187 (10) [M + H]+, 173 (23), 157 (100), 117 (2),
91 (1).
HRMS (CI): m/z [M + H+] calcd for C12H11O2: 187.0759; found:
187.0682.
Triisopropyl[5-(triisopropylsilyl)pent-4-yn-1-yloxy]silane (21)
To a soln of triisopropyl(pent-4-yn-1-yloxy)silane (23)15 (480 mg,
1.99 mmol) in THF (10 mL) was slowly added n-BuLi (1.45 mL,
2.38 mmol, 1.6 M soln in hexanes) at –78 °C. The reaction mixture
was stirred for 10 min at r.t. and then TIPSCl (0.51 mL, 2.38 mmol)
was added at –78 °C. The mixture was warmed to r.t. and stirred for
2 h. The resulting mixture was quenched with sat. NH4Cl soln (10
mL) and extracted with Et2O (2 × 20 mL). The combined organic
layer was washed with brine (20 mL), dried over MgSO4, filtered
and concentrated. The residue was purified by column chromatog-
raphy on silica gel (hexane–EtOAc, 20:1) to give 21 as a colorless
oil; yield: 590 mg (74%).
IR (CHCl3): 2942, 2865, 2172, 1463, 1109 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.01–1.17 (m, 42 H) 1.73 (quin,
J = 6.4 Hz, 2 H), 2.35 (t, J = 6.8 Hz, 2 H), 3.80 (t, J = 6.1 Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = 11.3 (3 C), 12.0 (3 C), 16.2, 18.0
(6 C), 18.6 (6 C), 32.2, 61.8, 80.0, 108.7.
Pent-4-yn-1-yl Pivalate (15)7a
Starting from 7 (120 mg, 0.370 mmol), compound 15 was isolated
as a colorless oil (eluent: hexane–EtOAc, 10:1); yield: 54 mg
(86%). The title compound is known, but physical and spectral data
were not previously reported.
IR (CHCl3): 3303, 2963, 2933, 1729, 1157 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.17 (s, 9 H), 1.83 (quin, J = 6.5
Hz, 2 H), 1.94 (t, J = 2.5 Hz, 1 H), 2.26 (dt, J = 7.1, 2.7 Hz, 2 H),
4.12 (t, J = 6.4 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 15.1, 27.1 (3 C), 27.6, 38.7, 62.8,
68.9, 83.0, 178.4.
MS (CI): m/z (%) = 397 (12) [M + H]+, 354 (41), 353 (100), 311
(17).
HRMS (CI): m/z [M + H+] calcd for C23H49OSi2: 397.3322; found:
397.3323.
Triisopropyl[4-(triisopropylsilylethynyl)benzyloxy]silane (22)8a
Spectroscopic data were identical to those reported.
MS (CI): m/z (%) = 169 (100) [M + H]+, 165 (21), 131 (12), 103
(20), 57 (76).
1H NMR (300 MHz, CDCl3): d = 1.06–1.15 (m, 42 H), 4.82 (s, 2 H),
7.29 (d, J = 8.4 Hz, 2 H), 7.45 (d, J = 8.4 Hz, 2 H).
HRMS (CI): m/z [M + H+] calcd for C10H17O2: 169.1228; found:
169.1228.
Undec-10-yn-1-yl Acetate (16)16
Desilylation of 1-(Triisopropylsilyl)acetylenes; General Proce-
dure
Starting from 8 (112 mg, 0.300 mmol), compound 16 was isolated
as a colorless oil (eluent: hexane–EtOAc, 10:1); yield: 61 mg
(96%). The title compound is known, but physical and spectral data
were not previously reported.
To a stirred soln of 1-(triisopropylsilyl)acetylene (1.0 equiv, 0.1 M
in MeCN or DMF), AgF (1.5 equiv) was added in the dark. The re-
action mixture was stirred at r.t. for 3 h and then 1 M HCl (2.0
equiv) was added. The mixture was stirred for 5 min, diluted with
Et2O (10 mL) then washed with H2O (5 mL), dried over MgSO4 and
filtered through a pad of Celite. The filtrate was concentrated in vac-
uo and the residue was purified by column chromatography on sili-
ca gel (hexane–EtOAc; detection: UV and KMnO4) to afford the
terminal alkyne.
IR (CHCl3): 3302, 2931, 2857, 1739, 1241 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.19–1.38 (m, 10 H), 1.48 (quin,
J = 6.7 Hz, 2 H), 1.57 (quin, J = 6.7 Hz, 2 H), 1.90 (t, J = 2.7 Hz, 1
H), 2.01 (s, 3 H), 2.14 (dt, J = 6.9, 2.5 Hz, 2 H), 4.01 (t, J = 6.7 Hz,
2 H).
13C NMR (100 MHz, CDCl3): d = 18.3, 20.9, 25.8, 28.3, 28.5, 28.9,
29.1, 29.2, 64.6, 68.0, 84.6, 104.1, 171.1.
MS (CI): m/z (%) = 212 (14), 211 (100) [M + H]+, 169 (24), 151
(37), 95 (31).
[(Pent-4-yn-1-yloxy)methyl]benzene (2)11
Starting from 3 (95.0 mg, 0.290 mmol), compound 2 was isolated
as a colorless oil (eluent: hexane–EtOAc, 15:1); yield: 48 mg
(92%). The title compound is known, but physical and spectral data
were not previously reported.
HRMS (CI): m/z [M + H+] calcd for C13H23O2: 211.1698; found:
211.1694.
Synthesis 2009, No. 12, 1963–1968 © Thieme Stuttgart · New York

1968
S. Kim et al.
PAPER
[(Pent-4-yn-1-yloxy)methanetriyl]tribenzene (17)13
Starting from 9 (97.0 mg, 0.200 mmol), compound 17 was isolated
as a white solid (eluent: hexane–EtOAc, 20:1); yield: 60 mg (80%);
mp 77–79 °C. A yield of 91% was obtained when the reaction was
hydrolyzed using sat. aq NH4Cl soln. Spectroscopic data were iden-
tical to those reported.
1H NMR (400 MHz, CDCl3): d = 1.85 (quin, J = 6.4 Hz, 2 H), 1.90
(t, J = 2.6 Hz, 1 H), 2.37 (dt, J = 7.3, 2.6 Hz, 2 H), 3.20 (t, J = 6.1
Hz, 2 H), 7.24 (t, J = 7.2 Hz, 3 H), 7.31 (t, J = 7.25 Hz, 6 H), 7.47
(d, J = 7.4 Hz, 6 H).
References
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13C NMR (100 MHz, CDCl3): d = 15.5, 29.1, 61.9, 68.3, 84.1, 86.3,
126.8 (3 C), 127.6 (6 C), 128.6 (6 C), 144.2 (3 C).
tert-Butyl (4S)-4-[(1R)-1-Hydroxyprop-2-yn-1-yl]-2,2-dimeth-
yl-1,3-oxazolidine-3-carboxylate (18)17
Starting from 10 (50.0 mg, 0.120 mmol), compound 18 was isolated
as a colorless oil (eluent: hexane–EtOAc, 5:1); yield: 29 mg, (94%).
Spectroscopic data were identical to those reported.
1H NMR (300 MHz, CDCl3): d = 1.47 (s, 9 H), 1.58 (s, 6 H), 2.41
(s, 1 H), 3.38 (m, 1 H), 4.06 (m, 1 H), 4.11 (br s, 1 H), 4.14 (m, 1 H).
(4-Ethynylphenyl)methanol (19)18
Starting from 11 (80.0 mg, 0.250 mmol), compound 19 was isolated
as a colorless oil (eluent: hexane–EtOAc, 3:1); yield: 30 mg (92%).
Spectroscopic data were identical to those reported.
1H NMR (300 MHz, CDCl3): d = 2.00 (s, 1 H), 3.05 (s, 1 H), 4.64
(s, 2 H), 7.27 (d, J = 8.3 Hz, 2 H), 7.45 (d, J = 8.3 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 64.7, 77.1, 83.4, 121.2, 126.6 (2
(5) (a) Brossat, M.; Heck, M. P.; Mioskowski, C. J. Org. Chem.
2007, 72, 5938. (b) Jung, M. E.; Hagenah, J. A. J. Org.
Chem. 1987, 52, 1889. (c) Churcher, I.; Hallett, D.; Magnus,
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(6) Schmidt, H. M.; Arens, J. F. Recl. Trav. Chim. Pays-Bas.
1967, 86, 1138.
C), 132.2 (2 C), 141.5.
[(Penta-2,4-diyn-1-yloxy)methyl]benzene (20)8a
Starting from 12 (53.0 mg, 0.160 mmol), compound 20 was isolated
as a colorless oil (eluent: hexane–EtOAc, 10:1); yield: 26 mg
(97%). Spectroscopic data were identical to those reported.
(7) (a) Orsini, A.; Vitérisi, A.; Bodlenner, A.; Weibel, J.-M.;
Pale, P. Tetrahedron Lett. 2005, 46, 2259. (b) Carpita, A.;
Mannocci, L.; Rossi, R. Eur. J. Org. Chem. 2005, 1859.
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1H NMR (300 MHz, CDCl3): d = 2.17 (s, 1 H), 4.21 (s, 2 H), 4.59
(s, 2 H), 7.29–7.35 (m, 5 H).
13C NMR (100 MHz, CDCl3): d = 57.3, 67.5, 68.0, 70.6, 71.8, 72.6,
128.0, 128.1 (2 C), 128.4 (2 C), 136.9.
Triisopropyl(pent-4-yn-1-yloxy)silane (23)15
Starting from 21 (77.0 mg, 0.190 mmol), compound 23 was isolated
as a colorless oil (eluent: hexane–EtOAc, 15:1); yield: 41 mg
(90%). Spectroscopic data were identical to those reported.
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Lett. 2001, 3, 4107. (b) Arnold, M. A.; Day, K. A.; Duron, S.
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1H NMR (300 MHz, CDCl3): d = 0.99–1.12 (m, 21 H), 1.73 (quin,
J = 7.1 Hz, 2 H), 1.90 (t, J = 2.5 Hz, 1 H), 2.28 (dt, J = 7.1, 2.8 Hz,
2 H), 3.75 (t, J = 6.0 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 12.0 (3 C), 14.9, 18.0 (6 C), 31.8,
61.7, 68.1, 84.4.
(4-Ethynylbenzyloxy)triisopropylsilane (24)19
Starting from 22 (100 mg, 0.220 mmol), compound 24 was isolated
as a colorless oil (eluent: hexane–EtOAc, 20:1); yield: 59 mg
(94%). Spectroscopic data were identical to those reported.
(15) Ishiyama, H.; Takemura, T.; Tsuda, M.; Kobayashi, J.
Tetrahedron 1999, 55, 4583.
1H NMR (300 MHz, CDCl3): d = 1.02–1.17 (m, 21 H), 3.02 (s, 1 H),
4.81 (s, 2 H), 7.29 (d, J = 8.4 Hz, 2 H), 7.44 (d, J = 8.2 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 12.0 (3 C), 18.0 (6 C), 64.6, 76.5,
(16) (a) Yoshida, M.; Yoshikawa, S.; Fukuhara, T.; Yoneda, N.;
Hara, S. Tetrahedron 2001, 57, 7143. (b) Ochiai, M.;
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83.8, 120.3, 125.5 (2 C), 132.0 (2 C), 142.5.
Acknowledgment
(19) Nguyen, N. H.; Apriletti, J. W.; Baxter, J. D.; Scanlan, T. S.
J. Am. Chem. Soc. 2005, 127, 4599.
This work was supported by the Korea Science and Engineering
Foundation (KOSEF) through the National Research Laboratory
Program funded by the Ministry of Science and Technology
(M10500000055–06J0000–05510).
Synthesis 2009, No. 12, 1963–1968 © Thieme Stuttgart · New York