Facile one-pot syntheses of bromoacetylenes from bulky trialkylsilyl acetylenes

Article abstract of DOI:10.1016/j.tet.2006.02.016

Because haloalkynes are versatile intermediates in synthetic chemistry, the development of new efficient methods for the conversion of 1-trialkylsilylacetylenes to haloacetylenes in situ remains desirable, especially when the corresponding terminal acetyl

Full text of DOI:10.1016/j.tet.2006.02.016

Tetrahedron 62 (2006) 4081–4085
Facile one-pot syntheses of bromoacetylenes from bulky
trialkylsilyl acetylenes
Taeho Lee,b Hee Ryong Kang,a Shinae Kima,b and Sanghee Kima,b,
*
aCollege of Pharmacy, Seoul National University, San 56-1, Shilim, Kwanak, Seoul 151-742, Korea
bNatural Products Research Institute, College of Pharmacy, Seoul National University, 28 Yungun, Jongro, Seoul 110-460, Korea
Received 6 December 2005; revised 3 February 2006; accepted 6 February 2006
Available online 6 March 2006
Abstract—Because haloalkynes are versatile intermediates in synthetic chemistry, the development of new efficient methods for the
conversion of 1-trialkylsilylacetylenes to haloacetylenes in situ remains desirable, especially when the corresponding terminal acetylenes are
unstable. Using AgF and NBS, we have successfully transformed various 1-(trialkylsilyl)acetylenes, including bulky trialkylsilyl acetylenes,
into bromoacetylenes in high yield. The reactions are chemoselective: triisopropylsilyl ethers were not deprotected under these conditions.
q 2006 Elsevier Ltd. All rights reserved.
1. Introduction
As part of our ongoing program aimed at the preparation of
unsymmetrical polyynes for use in the syntheses of natural
products and organic materials, we needed a method to
convert 1-(trialkylsilyl)acetylenes into bromoacetylenes.
Conceivably, this transformation could be achieved by a
protiodesilylation of silyl-protected acetylenes and sub-
sequent halogenation of the resulting terminal acetylenes.4
Although effective methods are available for this two-step
sequence, the major limitation of this conventional
approach is the instability of many terminal acetylenes,
especially terminal diynes and higher polyynes.1a,5 To avoid
the complications encountered when attempting to isolate
sensitive terminal alkynes, we preferred to employ an in situ
one-pot desilylative bromination.
Haloalkynes are useful and versatile intermediates in a
variety of organic transformations. They can be used as
precursors for the generation of organometallic acetylides,
a-keto acid esters, vinyl halides, vinyl organometallic
compounds, and other functional groups (Fig. 1);1 they
can also been used as substrates for a variety of metal-
mediated coupling reactions.2 One of the most convenient
approaches to the preparation of haloalkynes is the
halogenation of terminal acetylenes.3
O
X
R
OMe
M
R
R
O
In 1994, Isobe and co-workers reported the direct
conversion of trimethylsilyl (TMS)-protected acetylenes to
haloacetylenes through the use of a catalytic amount of
AgNO3 and a halogen source, such as NBS or NIS.6 This
convenient method, which is mild enough to accommodate
substrates possessing many different functionalities, has
been applied widely in the synthetic community.7 Unfortu-
nately, this system is effective only for TMS-protected
acetylenes and not for bulkier (trialkylsilyl)acetylenes,4,7a
presumably because of the increased stability of bulkier silyl
groups. Under similar conditions, the use of the more highly
soluble CF3CO2Ag and NBS also leads to the direct
desilylative bromination of TMS- and (hydroxypropyl)-
silyl-protected acetylenes.8
Metal-mediated
coupling
M
R
R
X
1-haloalkyne
R = alkyl, aryl, etc.
X = Cl, Br, I
M = Li, Sn, B, Zr, Al, etc.
Figure 1. Reaction of haloalkynes.
Keywords: Haloalkyne; Trialkylsilyl acetylene; Desilylative bromination;
AgF.
*
Corresponding author. Address: Natural Products Research Institute,
College of Pharmacy, Seoul National University, 28 Yungun, Jongro,
Seoul 110-460, Korea. Tel.: C82 2 740 8913; fax: C82 2 762 8322;
e-mail: pennkim@snu.ac.kr
Although less-bulky silyl groups, such as TMS or
triethylsilyl (TES) units, are used classically as protecting
groups for terminal acetylenes, relatively bulkier
0040–4020/$ - see front matter q 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.02.016

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T. Lee et al. / Tetrahedron 62 (2006) 4081–4085
trialkylsilyl protecting groups are also very useful syntheti-
cally because the more sterically hindered carbon–carbon
triple bonds and carbon–silicon single bonds are inert
toward a variety of reagents.9 As far as we are aware, the
direct desilylative bromination of bulky 1-trialkylsilyl-
acetylenes has not been reported previously.10 In this
paper, we present what we believe to be the first example of
a technique for the in situ conversion of bulky 1-(trialkyl-
silyl)acetylenes into 1-bromoacetylenes.11
Although this NBS/TBAF system permits the facile
direct desilylative bromination of bulky 1-(trialkylsilyl)-
acetylenes, the basicity of TBAF and use of excess NBS
could limit functional group tolerance. Thus, we needed to
develop alternative conditions for the reaction. Exposure of
1a to inorganic fluoride sources, namely CsF, NaF, and AlF3
(entries 7–9), in the presence of a catalytic amount of
AgNO3 and a slight excess of NBS (1.2 equiv) in MeCN
resulted in the recovery of the starting material only. On the
other hand, when we employed AgF as the fluoride source
we obtained the desired bromoacetylene 3 in 99% yield at
room temperature (entry 10). Because the redundancy of the
additional silver ions in the AgNO3/AgF/NBS system, we
found that AgNO3 could be removed from the system to
give the desired product 3 in 95% yield (entry 11).
2. Results and discussion
As expected, our initial attempts to effect the in situ
desilylative bromination of triisopropylsilyl (TIPS)-
protected acetylene 1a11 using Isobe’s standard NBS/
AgNO3 conditions (entry 1, Table 1) led to the recovery
only of the starting material. The addition of an oxygenated
base, such as NaOH in acetone and K2CO3 in THF (entries 2
and 3), to the NBS/AgNO3 mixture also proved futile.
Therefore, we chose to use a fluoride source to remove the
bulky TIPS group, triggered by the known high affinity of
fluoride ions toward silicon atoms. When using a
commercial THF solution of tetrabutylammonium fluoride
(TBAF) in the presence of a catalytic amount of AgNO3
(0.1 equiv) and a slight excess of NBS (1.2 equiv) in DMF,
protiodesilylation occurred, instead of the expected desily-
lative bromination, to give the terminal acetylene 2 in 73%
yield (entry 4). Employing a large excess of NBS (4 equiv),
however, led to the formation of the desired bromoacetylene
311 in high yield (95%) either in the presence or absence of
AgNO3 (entries 5 and 6, respectively).
To explore the scope of this AgF/NBS reaction system, we
examined the use of other solvents and substrates. Among
the solvents examined, DMF gave similar results (91%
yield, entry 12) to those obtained using MeCN, but the use
of acetone, DMSO, and THF did not yield the desired
product 3 presumably because of the low solubility of AgF
in those solvents (entries 13–15). Under the optimal reaction
conditions (AgF/NBS/MeCN), the acetylenes 1b and 1c,
which contained TBS and TES protecting groups, respect-
ively, were also smoothly converted to the bromoacetylene
3 in very high yields (entries 16 and 17). Moreover, this
system was also effective for converting other substrates (4a
and 4b) into their corresponding bromoacetylenes (5a12 and
5b) in good yields (Scheme 1).
Most interestingly, this AgF/NBS reaction system is
chemoselective.13 Under the optimized conditions, the
Table 1. Desilylative bromination of 1-trialkylsilyl acetylenesa
NBS, rt
R
H
or Br
condition
OBn
OBn
OBn
2
3
1a (R = TIPS)
1b (R = TBS)
1c (R = TES)
Entry
Reactant
Catalyst
Reagent
NBS (equiv)
Solvent
Product
Yield (%)b
1
2
3
4
5
6
7
8
1a (RZTIPS)
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
—
AgNO3
AgNO3
AgNO3
AgNO3
—
—
—
—
—
—
—
—
1.2
1.2
1.2
1.2
4.0
4.0
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
Acetone
Acetone
THF
DMF
DMF
DMF
MeCN
MeCN
MeCN
MeCN
MeCN
DMF
Acetone
DMSO
THF
ndc
nd
nd
2
3
3
nd
nd
nd
3
3
3
—
—
—
73
95
95
—
—
—
99
95
91
—
—
—
91
95
NaOH
K2CO3
TBAF
TBAF
TBAF
CsF
NaF
AlF3
AgF
AgF
AgF
AgF
AgF
AgF
AgF
AgF
9
10
11
12
13
14
15
16
17
nd
nd
nd
3
1a
1b (RZTBS)
1c (RZTES)
MeCN
MeCN
3
a All reactions were performed on 0.1–0.3 mmol scale. Conditions; 0.1 equiv of catalyst, room temperature, 2–3 h.
b Isolated yield.
c ndZnot dectected.

T. Lee et al. / Tetrahedron 62 (2006) 4081–4085
4083
The reaction mixture was stirred for 2 h at room temperature
and then quenched with saturated NH4Cl solution. The
mixture was diluted with ether, washed with brine, dried
over Na2SO4, filtered, and concentrated in vacuo. The
resulting residue was purified by column chromatography
on silica gel (hexane/EtOAc, 50:1 or 100:1) to give 1-
(trialkylsilyl)diyne 1.
NBS, AgF
TIPS
Br
MeCN, 3 h, rt
R
R
4a (R=m-OMe)
4b (R =p-CH2OH)
5a (R =m-OMe, 84%)
5b (R =p-CH2OH, 83%)
Scheme 1.
4.1.1.1. 1-(Triisopropylsilyl)-5-(benzyloxy)penta-1,3-
diyne (1a). As a yellow oil (131 mg, 91%) from 1-bromo-
TIPS-protected acetylenes 6 and 8, which also contained
TIPS-protected hydroxyl groups, formed their correspond-
ing bromoacetylenes 7 and 9 in very high yields without any
notable O-silyl group removal (Scheme 2).
1
3-(benzyloxy)prop-1-yne (100 mg, 0.44 mmol): H NMR
(300 MHz, CDCl3) d 1.11 (s, 21H), 4.25 (s, 2H), 4.62 (s,
2H), 7.31–7.38 (m, 5H); 13C NMR (75 MHz, CDCl3) d 11.2,
18.5, 57.6, 71.7, 71.8, 72.9, 84.4, 88.9, 127.9, 128.1, 128.4,
137.1; MS (EI) m/z (rel int.) 326 (MC, 1), 284 (68), 141
(56), 91 (100); HRMS (EI) calcd for C21H30OSi (MC)
326.2066, found 326.2066.
NBS, AgF
TIPS
Br
MeCN, 3 h, rt
95%
TIPSO
TIPSO
6
7
4.1.1.2. 1-(tert-Butyldimethylsilyl)-5-(benzyloxy)-
penta-1,3-diyne (1b). As a yellow oil (789 mg, 89%)
OTIPS
OTIPS
NBS, AgF
from
1-bromo-3-(benzyloxy)prop-1-yne
(697 mg,
1
3.10 mmol): H NMR (300 MHz, CDCl3) d 0.18 (s, 6H),
0.99 (s, 9H), 4.25 (s, 2H), 4.62 (s, 2H), 7.31–7.39 (m, 5H);
13C NMR (75 MHz, CDCl3) d K4.9, 16.7, 26.0, 57.5, 71.5,
71.7, 73.5, 85.8, 87.9, 127.9, 128.0, 128.4, 137.1; MS (EI)
m/z (rel int.) 284 (MC, 2), 227 (42), 139 (87), 91 (100);
HRMS (CI) calcd for C18H23OSi ([MCH]C) 283.1518,
found 283.1513.
MeCN, 3 h, rt
96%
TIPS
Br
9
8
Scheme 2.
3. Conclusion
In conclusion, we have developed an efficient method for
the in situ conversion of 1-(trialkylsilyl)acetylenes to
bromoacetylenes through the addition of a fluoride source
to Isobe’s standard NBS/AgC conditions. The optimized
reaction conditions (AgF and NBS in MeCN or DMF)
afforded high yields of bromoacetylenes from various
substrates. This new method provides efficient access to
synthetically useful haloalkynes, especially when unstable
terminal acetylenes are involved.
4.1.1.3. 1-(Triethylsilyl)-5-(benzyloxy)penta-1,3-diyne
(1c). As a yellow oil (589 mg, 93%) from 1-bromo-3-
(benzyloxy)prop-1-yne (500 mg, 2.23 mmol): 1H NMR
(300 MHz, CDCl3) d 0.69 (q, JZ7.8 Hz, 6H), 1.06 (t, JZ
7.8 Hz, 9H), 4.26 (s, 2H), 4.63 (s, 2H), 7.33–7.39 (m, 5H);
13C NMR (75 MHz, CDCl3) d 4.0, 7.2, 57.4, 71.5, 71.6,
73.3, 85.1, 88.3, 127.8, 128.0, 128.3, 137.0; MS (EI) m/z (rel
int.) 284 (MC, 1), 255 (91), 227 (97), 197 (51), 169 (50), 91
(100); HRMS (CI) calcd for C18H25OSi ([MCH]C)
285.1675, found 285.1671.
4. Experimental
4.1. General
4.1.2. 5-(Benzyloxy)penta-1,3-diyne (2). To a solution of
1a (100 mg, 0.31 mmol) in DMF (3 mL) were added NBS
(66 mg, 0.37 mmol), TBAF (0.37 mL, 0.37 mmol, 1.0 M
solution in THF) and AgNO3 (5.2 mg, 0.031 mmol). The
reaction mixture was stirred for 3 h at room temperature and
then quenched with saturated NH4Cl solution. The mixture
was diluted with ether, washed with brine, dried over
Na2SO4, filtered, and concentrated in vacuo. The resulting
residue was purified by column chromatography on silica
gel (hexane/EtOAc, 50:1) to give 2 (39 mg, 73%) as a
yellow oil: 1H NMR (300 MHz, CDCl3) d 2.19 (t, JZ
0.9 Hz, 1H), 4.23 (d, JZ1.2 Hz, 2H), 4.61 (s, 2H), 7.30–
7.38 (m, 5H); 13C NMR (75 MHz, CDCl3) d 57.3, 67.5,
68.0, 70.6, 71.8, 72.6, 128.0, 128.1, 128.4, 136.9; MS (CI)
m/z (rel int.) 169 ([MK1]C, 20), 153 (62), 141 (100), 91
(94); HRMS (CI) calcd for C12H9O ([MKM]C) 169.0653,
found 169.0657.
All reagents and solvents were purchased from commercial
sources and used without further purification unless
otherwise stated. Reactions were monitored through TLC
analysis using Merck silica gel 60 F-254 thin layer plates.
Flash column chromatography was carried out on Merck
silica gel 60 (230–400 mesh). Compounds were visualized
on TLC plates under UV light and by spraying with KMnO4
or anisaldehyde solutions. Melting points are uncorrected.
1H and 13C NMR spectra were recorded in d units relative to
deuterated solvent as internal reference by Varian 300 MHz
NMR instrument. Mass spectra (MS) were recorded at 70 or
30 eV using electron impact (EI) and chemical ionization
(CI). High-resolution mass spectra (HRMS) were recorded
using EI and CI.
4.1.1. General procedure for preparing 1-(trialkylsilyl)-
diynes (1). To a degassed solution of 1-bromo-3-(benzyl-
oxy)prop-1-yne3,11,14 (1.0 equiv), (trialkylsilyl)acetylene
(1.2 equiv), Pd(PPh3)2Cl2 (0.01 equiv) and CuI (0.01 equiv)
in THF (0.3 M) was added diisopropylamine (2.0 equiv).
4.1.3. General procedures for the desilylative bromina-
tion. Method A. To a solution of the 1-(trialkylsilyl)acety-
lene (1.0 equiv) in DMF (0.3 M) were added NBS
(4.0 equiv), TBAF (1.2 equiv) and AgNO3 (0.1 equiv).
The reaction mixture was stirred for 3 h at room temperature

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T. Lee et al. / Tetrahedron 62 (2006) 4081–4085
and then quenched with saturated NH4Cl solution. The
mixture was diluted with ether, washed with brine, dried
over Na2SO4, filtered, and concentrated in vacuo. The
resulting residue was purified by column chromatography
on silica gel to give the 1-bromoalkyne.
4.1.6. 1-Bromo-2-(3-methoxyphenyl)ethyne (5a).
Following the same procedure as for desilylative bromina-
tion method B. As a colorless oil (109 mg, 84%) from 4a
1
(177 mg, 0.61 mmol): H NMR (300 MHz, CDCl3) d 3.80
(s, 3H), 6.90 (ddd, JZ1.2, 2.7, 8.1 Hz, 1H), 6.98 (dd, JZ
1.2, 2.7 Hz, 1H), 7.05 (ddd, JZ1.2, 1.2, 7.8 Hz, 1H), 7.22
(app. t, JZ8.0 Hz, 1H); 13C NMR (75 MHz, CDCl3) d 49.6,
55.2, 79.9, 115.3, 116.8, 123.6, 124.4, 129.3, 159.2; MS (EI)
m/z (rel int.) 210 (MC, 16), 181 (32), 131 (27), 102 (100);
HRMS (CI) calcd for C9H8OBr ([MCH]C) 210.9758,
found 210.9761.
Method B. To a solution of the 1-(trialkylsilyl)acetylene
(1.0 equiv) in acetonitrile (0.1 M) were added NBS
(1.2 equiv) and AgF (1.2 equiv) in the dark. The reaction
mixture was stirred at room temperature for 2–3 h and then
filtered through a pad of Celite. The filtrate was diluted with
ether, washed with water, dried over Na2SO4, filtered, and
concentrated in vacuo. The resulting residue was purified by
column chromatography on silica gel to give the
1-bromoalkyne.
4.1.7. 1-Bromo-2-[4-(hydroxymethyl)phenyl]ethyne (5b).
Following the same procedure as for desilylative bromina-
tion method B. As a white solid (162 mg, 83%) from 4a
1
(267 mg, 0.93 mmol): mp 75–76 8C; H NMR (300 MHz,
4.1.3.1. 1-Bromo-5-(benzyloxy)penta-1,3-diyne (3).
Method A. As a yellow oil (83 mg, 95%) from 1a
(114 mg, 0.35 mmol).
CDCl3) d 1.70 (br s, 1H), 4.70 (s, 2H), 7.31 (d, JZ8.4 Hz,
2H), 7.45 (d, JZ8.4 Hz, 2H); 13C NMR (75 MHz, CDCl3) d
49.8, 64.4, 79.8, 121.6, 126.6, 132.0, 141.3; MS (EI) m/z (rel
int.) 210 (MC, 49), 181 (12), 131 (38), 102 (100); HRMS
(EI) calcd for C9H7OBr (MC) 210.9758, found 210.9758.
Method B. As a yellow oil (73 mg, 95%) from 1a (101 mg,
1
0.31 mmol): H NMR (300 MHz, CDCl3) d 4.22 (s, 2H),
4.60 (s, 2H), 7.32–7.37 (m, 5H); 13C NMR (75 MHz,
CDCl3) d 41.3, 57.4, 64.9, 71.39, 71.44, 71.8, 128.0, 128.1,
128.5, 136.9; MS (EI) m/z (rel int.) 248 (MC, 2), 218 (34),
139 (76), 91 (100); HRMS (EI) calcd for C12H9BrO (MC)
247.9837, found 247.9839.
4.1.8. 1-(Triisopropylsilyl)-1-[4-(triisopropylsilyloxy-
methyl)phenyl]ethyne (6). To a solution of 4b (113 mg,
0.40 mmol) in CH2Cl2 (4 mL) were added (triisopropylsi-
lyl)chloride (0.10 mL, 0.48 mmol) and imidazole (55 mg,
0.80 mmol) at 0 8C. The mixture was stirred at room
temperature for 1 h. The reaction mixture was quenched
with 1% Na2CO3 solution and extracted with hexane
(10 mL!2). The combined organic layers were washed
with water (20 mL) and brine (20 mL), dried over Na2SO4,
filtered, and concentrated under reduced pressure. The
residue was purified by silica gel chromatography (hexane/
EtOAc, 100:1) to give 6 (167 mg, 94%) as a colorless oil: 1H
NMR (300 MHz, CDCl3) d 1.06–1.15 (m, 42H), 4.82 (s,
2H), 7.29 (d, JZ8.4 Hz, 2H), 7.45 (d, JZ8.4 Hz, 2H); 13C
NMR (75 MHz, CDCl3) d 11.3, 12.0, 18.0, 18.7, 64.8, 89.8,
107.3, 121.9, 125.4, 131.9, 142.0; MS (EI) m/z (rel int.) 444
(MC, 4), 401 (100), 271 (23); HRMS (CI) calcd for
C27H49OSi2 ([MCH]C) 445.3322, found 445.3331.
4.1.4. 1-(Triisopropylsilyl)-2-(3-methoxyphenyl)ethyne
(4a). Following the same procedure as for 1, from 3-iodo-
anisole (200 mg, 1.02 mmol) in THF (10 mL), (triisopropyl-
silyl)acetylene (0.24 mL, 1.2 mmol), Pd(PPh3)2Cl2 (18 mg,
0.03 mmol), CuI (4.8 mg, 0.03 mmol) and diisopropylamine
(0.25 mL, 1.8 mmol), after a reaction time of 2 h, 4a (190 mg,
1
77%) was obtained as a yellow oil: H NMR (300 MHz,
CDCl3) d 1.13 (s, 21H), 3.81 (s, 3H), 6.87 (ddd, JZ1.2, 2.7,
8.4 Hz, 1H), 6.99 (dd, JZ1.2, 2.7 Hz, 1H), 7.08 (ddd, JZ1.2,
1.2, 7.2 Hz, 1H), 7.20 (app. t, JZ7.8 Hz, 1H); 13C NMR
(75 MHz, CDCl3) d 11.3, 18.7, 55.3, 90.3, 107.0, 114.9,
116.8, 124.5, 124.6, 129.2, 159.2; MS (EI) m/z (rel int.) 288
(MC, 20), 245 (88), 217 (30), 203 (47), 189 (59), 175 (100),
94 (48); HRMS (CI) calcd for C18H29OSi ([MCH]C)
289.1988, found 289.1988.
4.1.9. 1-Bromo-2-[4-(triisopropylsilyloxymethyl)phenyl]-
ethyne (7). Following the same procedure as for desilylative
bromination method B. As a colorless oil (103 mg, 95%)
from 6 (131 mg, 0.29 mmol): 1H NMR (300 MHz, CDCl3) d
1.06–1.12 (m, 21H), 4.82 (s, 2H), 7.30 (d, JZ8.1 Hz, 2H),
7.42 (d, JZ8.1 Hz, 2H); 13C NMR (75 MHz, CDCl3) d 12.0,
18.0, 49.0, 64.6, 80.1, 120.9, 125.5, 131.8, 142.4; MS (EI) m/z
(rel int.) 366 (MC, 3), 325 (100), 253 (15), 193 (92), 114 (53);
HRMS (EI) calcd for C18H28OBrSi ([MCH]C) 367.1092,
found 367.1096.
4.1.5. 1-(Triisopropylsilyl)-2-[4-(hydroxymethyl)phenyl]-
ethyne (4b). To a solution of 4-bromobenzyl alcohol
(500 mg, 2.67 mmol), (triisopropylsilyl)acetylene (0.72 mL,
3.20 mmol), PdCl2(PhCN)2 (31 mg, 0.08 mmol), CuI (10 mg,
0.05 mmol), and tri-tert-butylphosphine (0.037 mL,
0.16 mmol) in dioxane (6 mL) was added diisopropylamine
(0.45 mL, 3.20 mmol). The reaction mixture was stirred for
4 h at room temperature. The reaction mixture diluted with
hexane, filtered through Celite, and concentrated in vacuo.
The resulting residue was purified by column chromato-
graphy on silica gel (hexane/EtOAc, 10:1) to give 4b
(750 mg, 97%) as a colorless oil: 1H NMR (300 MHz,
CDCl3) d 1.13 (s, 21H), 1.73 (t, JZ5.7 Hz, 1H), 4.69 (d, JZ
5.7 Hz, 2H), 7.30 (d, JZ8.4 Hz, 2H), 7.47 (d, JZ8.4 Hz, 2H);
13C NMR (75 MHz, CDCl3) d 11.3, 18.6, 64.5, 90.4, 106.9,
122.6, 126.6, 132.1, 141.0; MS (EI) m/z (rel int.) 288 (MC, 5),
245 (69), 217 (23), 203 (40), 189 (60), 175 (100), 115 (62);
HRMS (CI) calcd for C18H27OSi ([MKH]C) 287.1831,
found 287.1827.
4.1.10. 1-(Triisopropylsilyl)-3-(triisopropylsilyloxy)-3-
phenylprop-1-yne (8). To a solution of (triisopropylsilyl)-
acethylene (500 mg, 2.74 mmol) in THF (6 mL) was slowly
added n-BuLi (1.72 mL, 2.75 mmol, 1.6 M solution in
hexanes) at K40 8C. The reaction mixture was stirred for
30 min at K40 8C and then a solution of benzaldehyde
(278 mg, 2.74 mmol) in THF (3 mL) was added over 5 min.
The mixture was warmed to room temperature and stirred
for 3 h. The mixture was added saturated NH4Cl solution
at K40 8C and extracted with ether. The organic layer
was washed with brine, dried over Na2SO4, filtered,

T. Lee et al. / Tetrahedron 62 (2006) 4081–4085
4085
3. Abele, E.; Fleisher, M.; Rubina, K.; Abele, R.; Lukevics, E.
J. Mol. Catal. A: Chem. 2001, 165, 121–126 and references
cited therein.
and evaporated to dryness. The residue was purified by
column chromatography on silica gel (hexane/EtOAc, 10:1)
to give 1-phenyl-3-(triisopropylsilyl)prop-2-yn-1-ol15
(720 mg, 81%) as a colorless oil: 1H NMR (300 MHz,
CDCl3) d 1.09 (s, 21H), 5.49 (s, 1H), 7.30–7.41 (m, 3H),
7.57–7.60 (m, 2H). Following the same procedure as that
described for 6, from 1-phenyl-3-(triisopropylsilyl)prop-
2-yn-1-ol (235 mg, 0.82 mmol) in DMF (8 mL),
(triisoprophylsilyl)chloride (0.20 mL, 0.90 mmol), and
imidazole (140 mg, 2.10 mmol), after a reaction time of
1 h, compound 8 (331 mg, 91%) was obtained as a colorless
oil: 1H NMR (300 MHz, CDCl3) d 1.05–1.13 (m, 42H), 5.60
(s, 1H), 7.28–7.36 (m, 3H), 7.53 (d, JZ7.8 Hz, 2H); 13C
NMR (75 MHz, CDCl3) d 11.3, 12.4, 18.1, 18.5, 65.4, 86.2,
108.7, 126.1, 127.4, 128.1, 142.4; MS (EI) m/z (rel int.) 444
(MC, 1), 401 (100); HRMS (CI) calcd for C27H47OSi2
([MKH]C) 443.3165, found 443.3166.
4. Leibrock, B.; Vostrowsky, O.; Hirsch, A. Eur. J. Org. Chem.
2001, 4401–4409.
5. (a) Heuft, M. A.; Collins, S. K.; Yap, G. P. A.; Fallis, A. G.
Org. Lett. 2001, 3, 2883–2886. (b) Shi Shun, A. L. K.;
Chernick, E. T.; Eisler, S.; Tykwinski, R. R. J. Org. Chem.
2003, 68, 1339–1347. (c) Haley, M. M.; Bell, M. L.; Brand,
S. C.; Kimball, D. B.; Pak, J. J.; Wan, W. B. Tetrahedron Lett.
1997, 38, 7483–7486.
6. Nishikawa, T.; Shibuya, S.; Hosokawa, S.; Isobe, M. Synlett
1994, 485–486.
7. For the recent examples, see: (a) Tobe, Y.; Utsumi, N.;
Nagano, A.; Sonoda, M.; Naemura, K. Tetrahedron 2001, 57,
8075–8084. (b) Gung, B. W.; Kumi, G. J. Org. Chem. 2004,
69, 3488–3492. (c) Bellina, F.; Carpita, A.; Mannocci, L.;
Rossi, R. Eur. J. Org. Chem. 2004, 2610–2619. (d) See also
Ref. 4.
4.1.11. 1-Bromo-3-(triisopropylsilyloxy)-3-phenylprop-
1-yne (9). Following the same procedure as for desilylative
bromination method B. As a colorless oil (122 mg, 96%)
from 8 (153 mg, 0.34 mmol): 1H NMR (300 MHz, CDCl3) d
1.05–1.12 (m, 21H), 5.57 (s, 1H), 7.28–7.38 (m, 3H), 7.46–
7.49 (m, 2H); 13C NMR (75 MHz, CDCl3) d 12.2, 18.0,
45.7, 65.6, 83.2, 125.8, 127.8, 128.3, 141.5; MS (EI) m/z (rel
int.) 366 (MC, 1), 323 (27), 193 (38), 105 (100); HRMS (CI)
calcd for C18H28OBrSi ([MCH]C) 367.1092, found
367.1094.
8. Cai, C.; Vasella, A. Helv. Chim. Acta 1996, 79, 255–268.
9. Marino, J. P.; Nguyen, H. N. J. Org. Chem. 2002, 67,
6841–6844.
10. The desilylative bromination of 1-(phenylethynyl)silatrane has
been reported previously. See: Selina, A. A.; Karlov, S. S.;
Gauchenova, E. V.; Churakov, A. V.; Kuz’mina, L. G.;
Howard, J. A. K.; Lorberth, J.; Zaitseva, G. S. Heteroat. Chem.
2004, 15, 43–56.
11. Part of this work was published in preliminary form; see: Kim,
S.; Kim, S.; Lee, T.; Ko, H.; Kim, D. Org. Lett. 2004, 6,
3601–3604.
12. (a) Tsuchama, K.; Ogawa, T. Jpn. Kokai Tokkyo Koho,
JP04321643, 1992. (b) Verploegh, M. C.; Donk, L.; Bos,
H. J. T.; Drenth, W. Recl. Trav. Chim. Pays-Bas 1971, 90,
765–778.
Acknowledgements
This study was supported by the National Research
Laboratory Program (2005-01319), NRDP, Ministry of
Science and Technology, Republic of Korea.
13. For some recent examples of chemoselective silver-catalysed
protiodesilylation of TMS-protected acetylens, see: (a)
´
Orsini, A.; Viterisi, A.; Bodlenner, A.; Weibel, J.-M.; Pale,
P. Tetrahedron Lett. 2005, 46, 2259–2262. (b) Carpita, A.;
Mannocci, L.; Rossi, R. Eur. J. Org. Chem. 2005,
1859–1864.
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